Variant: NM_001083962.2(TCF4):c.850C>T (p.His284Tyr)

Version: 1.0
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CA357196

224133 (ClinVar)

Gene: TCF4 (HGNC:6925)

Condition: Pitt-Hopkins syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: 0b00488e-5915-4a4f-b331-26c1c3a95595

Approved on: 2023-12-06

Published on: 2023-12-11

HGVS expressions

NM_001083962.2:c.850C>T
NM_001083962.2(TCF4):c.850C>T (p.His284Tyr)
NC_000018.10:g.55269903G>A
CM000680.2:g.55269903G>A
NC_000018.9:g.52937134G>A
CM000680.1:g.52937134G>A
NC_000018.8:g.51088132G>A
NG_011716.1:g.323727C>T
NG_011716.2:g.371091C>T
ENST00000354452.8:c.850C>T
ENST00000630720.3:c.370C>T
ENST00000635822.2:c.850C>T
ENST00000635990.2:n.530C>T
ENST00000636400.2:c.778C>T
ENST00000636751.2:c.*558C>T
ENST00000636822.2:c.460C>T
ENST00000637115.2:c.*740C>T
ENST00000637169.2:c.202C>T
ENST00000637239.2:n.917C>T
ENST00000637250.2:n.544C>T
ENST00000637923.2:c.448C>T
ENST00000638154.3:c.880C>T
ENST00000643689.1:c.460C>T
ENST00000674764.1:c.*461C>T
ENST00000675707.1:c.460C>T
ENST00000354452.7:c.850C>T
ENST00000356073.8:c.850C>T
ENST00000398339.5:c.1156C>T
ENST00000457482.7:c.370C>T
ENST00000537578.5:c.778C>T
ENST00000537856.7:c.460C>T
ENST00000540999.5:c.778C>T
ENST00000543082.5:c.724C>T
ENST00000544241.6:c.637C>T
ENST00000561831.7:c.370C>T
ENST00000561992.5:c.460C>T
ENST00000562030.3:c.460C>T
ENST00000562607.5:c.460C>T
ENST00000562680.5:n.941C>T
ENST00000563686.5:n.705C>T
ENST00000563760.5:n.442C>T
ENST00000564228.5:c.637C>T
ENST00000564403.6:c.868C>T
ENST00000564999.5:c.850C>T
ENST00000565018.6:c.598C>T
ENST00000566279.5:c.670C>T
ENST00000566286.5:c.844C>T
ENST00000566514.5:c.811C>T
ENST00000567880.5:c.670C>T
ENST00000568673.5:c.778C>T
ENST00000568740.5:c.775C>T
ENST00000569012.5:c.460C>T
ENST00000570146.3:c.114C>T
ENST00000570177.6:c.460C>T
ENST00000570287.6:c.370C>T
ENST00000616053.4:c.598C>T
ENST00000625849.2:n.710C>T
ENST00000626584.2:c.202C>T
ENST00000627136.2:n.524-8370C>T
ENST00000628078.2:c.460C>T
ENST00000628636.2:c.460C>T
ENST00000628689.2:c.236C>T
ENST00000629343.2:c.460C>T
ENST00000629387.2:c.850C>T
ENST00000630268.2:c.460C>T
ENST00000630720.2:c.370C>T
ENST00000630828.2:c.640C>T
NM_001083962.1:c.850C>T
NM_001243226.2:c.1156C>T
NM_001243227.1:c.778C>T
NM_001243228.1:c.868C>T
NM_001243230.1:c.844C>T
NM_001243231.1:c.724C>T
NM_001243232.1:c.637C>T
NM_001243233.1:c.460C>T
NM_001243234.1:c.370C>T
NM_001243235.1:c.370C>T
NM_001243236.1:c.370C>T
NM_001306207.1:c.778C>T
NM_001306208.1:c.637C>T
NM_003199.2:c.850C>T
NM_001330604.2:c.850C>T
NM_001330605.2:c.460C>T
NM_001348211.1:c.724C>T
NM_001348212.1:c.460C>T
NM_001348213.1:c.460C>T
NM_001348214.1:c.370C>T
NM_001348215.1:c.202C>T
NM_001348216.1:c.370C>T
NM_001348217.1:c.778C>T
NM_001348218.1:c.778C>T
NM_001348219.1:c.778C>T
NM_001348220.1:c.775C>T
NM_001243226.3:c.1156C>T
NM_001243227.2:c.778C>T
NM_001243228.2:c.868C>T
NM_001243231.2:c.724C>T
NM_001243233.2:c.460C>T
NM_001243234.2:c.370C>T
NM_001243235.2:c.370C>T
NM_001243236.2:c.370C>T
NM_001330604.3:c.850C>T
NM_001330605.3:c.460C>T
NM_001348211.2:c.724C>T
NM_001348212.2:c.460C>T
NM_001348213.2:c.460C>T
NM_001348214.2:c.370C>T
NM_001348215.2:c.202C>T
NM_001348216.2:c.370C>T
NM_001348218.2:c.778C>T
NM_001348219.2:c.778C>T
NM_001369567.1:c.850C>T
NM_001369568.1:c.850C>T
NM_001369569.1:c.847C>T
NM_001369570.1:c.847C>T
NM_001369571.1:c.850C>T
NM_001369572.1:c.850C>T
NM_001369573.1:c.847C>T
NM_001369574.1:c.850C>T
NM_001369575.1:c.778C>T
NM_001369576.1:c.775C>T
NM_001369577.1:c.778C>T
NM_001369578.1:c.775C>T
NM_001369579.1:c.778C>T
NM_001369580.1:c.778C>T
NM_001369581.1:c.775C>T
NM_001369582.1:c.778C>T
NM_001369583.1:c.778C>T
NM_001369584.1:c.775C>T
NM_001369585.1:c.775C>T
NM_001369586.1:c.778C>T
NM_003199.3:c.850C>T
NM_001243230.2:c.844C>T

Uncertain Significance

• Not Met criteria codes: BA1 BS2 BS4 BS3 BS1 BP2 BP4 BP5 PS2 PS4 PS3 PS1 PP4 PP1 PP3 PM3 PM1 PM5 PM6 PM2

Expert Panel

Rett and Angelman-like Disorders VCEP

Criteria Specification Information

Criteria Specification: ClinGen Rett and Angelman-like Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for TCF4 Version 3.0.0

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The p.His284Tyr variant in TCF4 has been reported in an individual with a neurodevelopmental phenotype (PMID 28554332). The p.His284Tyr variant is present in two XY individuals in gnomAD v4 (0.0003%) (not sufficient to meet BS1 criteria). Computational prediction analysis tools are inconclusive for this variant. In summary, the p.His284Tyr variant in TCF4 is classified as a Variant of Unknown Significance based on the ACMG/AMP criteria (no criteria met).

Not Met criteria codes

• BA1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS1: The p.His284Tyr variant in TCF4 is present in 2 XY individuals in gnomAD v4 (0.0003%) (not sufficient to meet BS1 criteria)
• BP2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP5: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP4: The p.His284Tyr variant in TCF4 has been reported in an individual with a neurodevelopmental phenotype (PMID 28554332).
• PP1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP3: Computational prediction analysis tools are inconclusive for this variant
• PM3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM5: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM6: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline