Variant: NM_000138.5:c.2034_2052del

CA1139532474

Gene: FBN1

Condition: Marfan syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: f91d1ec7-8d8d-4100-a2ef-b70fa3f923c4

HGVS expressions

NM_000138.5:c.2034_2052del
NC_000015.10:g.48503854_48503872del
CM000677.2:g.48503854_48503872del
NC_000015.9:g.48796051_48796069del
CM000677.1:g.48796051_48796069del
NC_000015.8:g.46583343_46583361del
NG_008805.2:g.146923_146941del
ENST00000684448.1:n.708_726del
ENST00000316623.10:c.2034_2052del
ENST00000316623.9:c.2034_2052del
ENST00000537463.6:c.637-29216_637-29198del
NM_000138.4:c.2034_2052del

Likely Pathogenic

• Met criteria codes: PVS1 PM2

• Not Met criteria codes: BA1 BP1 BS4 BS3 BS1 BS2 PP2 PP1 PS4 PS1 PS3 PM5 PM1

Expert Panel

FBN1 VCEP

Criteria Specification Information

Criteria Specification: ClinGen FBN1 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 1

Evidence submitted by expert panel

FBN1 VCEP

The NM_00138 c.2034_2052del, is a frameshift variant in FBN1 predicted to cause a substitution of a threonine acid by alanine at amino acid 679 (p.Thr679Alafs*33). It is expected to cause a shift in the reading frame and likely results in an absent or disrupted protein product (PVS1). This variant has not been reported in ClinVar and has not been reported in the literature. 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

• BA1: PM2 is met
• BP1: Loss-of function variant
• 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: PM2 is met
• BS2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP2: Loss-of function variant
• PP1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS4: Not reported in the literature
• PS1: Loss-of function variant
• PS3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM5: Loss-of function variant
• PM1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Approved on: 2023-02-01

Published on: 2023-02-01