Variant: NM_006939.4(SOS2):c.3584C>T (p.Ala1195Val)

CA7176746

421233 (ClinVar)

Gene: SOS2

Condition: RASopathy

Inheritance Mode: Autosomal dominant inheritance

UUID: d5edfe96-0cd8-4104-af3c-015c6ea26247

Approved on: 2024-12-03

Published on: 2025-03-25

HGVS expressions

NM_006939.4:c.3584C>T
NM_006939.4(SOS2):c.3584C>T (p.Ala1195Val)
NC_000014.9:g.50118759G>A
CM000676.2:g.50118759G>A
NC_000014.8:g.50585477G>A
CM000676.1:g.50585477G>A
NC_000014.7:g.49655227G>A
NG_051073.1:g.117935C>T
ENST00000216373.10:c.3584C>T
ENST00000216373.9:c.3584C>T
ENST00000543680.5:c.3485C>T
NM_006939.2:c.3584C>T
NM_006939.3:c.3584C>T

Uncertain Significance

• Met criteria codes: BP4

• Not Met criteria codes: BS1 BA1 PM2

Expert Panel

RASopathy VCEP

Criteria Specification Information

Criteria Specification: ClinGen RASopathy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for SOS2 Version 2.3.0

Evidence submitted by expert panel

RASopathy VCEP

The c.3584C>T (NM_006939.4(SOS2):c.3584C>T (p.Ala1195Val)) variant in SOS2 is a missense variant predicted to cause substitution of alanine by valine at amino acid 1195. The filtering allele frequency in gnomAD v2.1.1 is 0.003446 % (no population codes met). The computational predictor REVEL gives a score of 0.183 which is below the threshold of 0.3, evidence that does not predict a damaging effect on SOS2 function (BP4). In summary, this variant meets the criteria to be classified as uncertain significance for autosomal dominant RASopathy, based on the ACMG/AMP criteria applied, as specified by the ClinGen RASopathy VCEP: BP4 (Version 2.3; 12/3/2024).

Met criteria codes

• BP4: The computational predictor REVEL gives a score of 0.183 which is below the threshold of 0.3, evidence that does not predict a damaging effect on SOS2 function (BP4).

Not Met criteria codes

• BS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BA1: The filtering allele frequency in gnomAD v2.1.1 is 0.003446 %. The highest MAF is 0.007027 % in the European (non-Finnish) population (no population codes met).
• PM2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline