NM_000138.5:c.6505G>T

CA269524632

Gene: FBN1

Condition: Marfan syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: e7e3d468-89e6-4afe-a059-f40529a03755

Approved on: 2023-02-01

Published on: 2023-02-01

HGVS expressions

NM_000138.5:c.6505G>T
NC_000015.10:g.48434705C>A
CM000677.2:g.48434705C>A
NC_000015.9:g.48726902C>A
CM000677.1:g.48726902C>A
NC_000015.8:g.46514194C>A
NG_008805.2:g.216084G>T
ENST00000682170.1:n.114G>T
ENST00000316623.10:c.6505G>T
ENST00000674301.1:n.1504G>T
ENST00000316623.9:c.6505G>T
ENST00000537463.6:c.*2268G>T
ENST00000559133.5:n.1812G>T
NM_000138.4:c.6505G>T

Likely Pathogenic

• Met criteria codes: PVS1 PM2

• Not Met criteria codes: BS1 PS4 PP1 PM1 BA1

Expert Panel

FBN1 VCEP

Criteria Specification Information

Evidence submitted by expert panel

FBN1 VCEP

The NM_00138 c.6506G>T, is a nonsense variant in FBN1 expected to cause a premature stop codon and likely results in an absent or disrupted protein product (PVS1). This variant has been previously reported in one individual with incomplete Marfan syndrome (PMID 17657824). This variant has not been reported in ClinVar. This variant is not present in gnomAD v2.1.1 (PM2_sup; https://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as likely pathogenic for Marfan syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen FBN1 VCEP: PVS1, PM2_supporting.

Met criteria codes

• PVS1: Predicted to cause NMD
• PM2: Absent in gnomad

Not Met criteria codes

• BS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS4: PS4 proband counting: 0.5 points. This variant has been previously reported in one individual with incomplete Marfan syndrome (PMID 17657824).
• PP1: Father known with aortic dissection, but carrier status unknown
• PM1: Affects a cb domain in cb-EGF but this argument should not be used with PVS1
• BA1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline