Variant: NM_000527.5(LDLR):c.694+25C>T

CA044382

251406 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

UUID: 56aaefac-d400-4477-a67e-91703e9a8be8

HGVS expressions

NM_000527.5:c.694+25C>T
NM_000527.5(LDLR):c.694+25C>T
NC_000019.10:g.11105625C>T
CM000681.2:g.11105625C>T
NC_000019.9:g.11216301C>T
CM000681.1:g.11216301C>T
NC_000019.8:g.11077301C>T
NG_009060.1:g.21245C>T
ENST00000558518.6:c.694+25C>T
ENST00000252444.9:n.948+25C>T
ENST00000455727.6:c.314-1767C>T
ENST00000535915.5:c.571+25C>T
ENST00000545707.5:c.314-940C>T
ENST00000557933.5:c.694+25C>T
ENST00000558013.5:c.694+25C>T
ENST00000558518.5:c.694+25C>T
ENST00000560467.1:n.294+25C>T
NM_000527.4:c.694+25C>T
NM_001195798.1:c.694+25C>T
NM_001195799.1:c.571+25C>T
NM_001195800.1:c.314-1767C>T
NM_001195803.1:c.314-940C>T
NM_001195798.2:c.694+25C>T
NM_001195799.2:c.571+25C>T
NM_001195800.2:c.314-1767C>T
NM_001195803.2:c.314-940C>T

Uncertain Significance

• Met criteria codes: BP4

• Not Met criteria codes: PM6 PM2 PM3 PM1 PM4 PM5 PVS1 BS4 BS3 BS1 BS2 BP2 BP3 BA1 PS2 PS4 PS3 PS1 PP4 PP1 PP3

Expert Panel

Familial Hypercholesterolemia VCEP

Criteria Specification Information

Criteria Specification: ClinGen Familial Hypercholesterolemia Expert Panel Specifications to the ACMG/AMP Variant Classification Guidelines Version 1.2

Evidence submitted by expert panel

Familial Hypercholesterolemia VCEP

The NM_000527.5(LDLR):c.694+25C>T variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence code BP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: BP4: The variant is not predicted to affect the splicing process by SpliceAI. So, BP4 is met.

Met criteria codes

• BP4: The variant is not predicted to affect the splicing process by SpliceAI. So, BP4 is met.

Not Met criteria codes

• PM6: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM2: PopMax MAF=0.00212 (0.212%) in Latino exomes+genomes (gnomAD v2.1.1).
• PM3: No data available
• PM1: Intronic variant
• PM4: No in-frame deletions/insertions
• PM5: Intronic variant
• PVS1: Not a null variant
• BS4: No data available
• BS3: No data available
• BS1: FAF=0.001766 (0.1766%) in Latino/Admixed American exomes+genomes (gnomAD v2.1.1).
• BS2: No data available
• BP2: No data available
• BP3: No in-frame deletions/insertions
• BA1: FAF=0.001766 (0.1766%) in Latino/Admixed American exomes+genomes (gnomAD v2.1.1).
• PS2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS4: Variant does not meet PM2
• PS3: No data available
• PS1: Intronic variant
• PP4: No data available
• PP1: No data available
• PP3: Intronic variant

Approved on: 2023-04-28

Published on: 2023-05-01