Variant: NM_002880.3(RAF1):c.1113T>C (p.Asp371=)

CA235339

180718 (ClinVar)

Gene: RAF1

Condition: RASopathy

Inheritance Mode: Autosomal dominant inheritance

UUID: ca1f922a-c651-4ca4-8afe-a28dde261256

Approved on: 2020-03-09

Published on: 2020-04-01

HGVS expressions

NM_002880.3:c.1113T>C
NM_002880.3(RAF1):c.1113T>C (p.Asp371=)
NM_001354689.1:c.1173T>C
NM_001354690.1:c.1113T>C
NM_001354691.1:c.870T>C
NM_001354692.1:c.870T>C
NM_001354693.1:c.1014T>C
NM_001354694.1:c.930T>C
NM_001354695.1:c.771T>C
NR_148940.1:n.1641T>C
NR_148941.1:n.1587T>C
NR_148942.1:n.1526T>C
NM_001354689.3:c.1173T>C
NM_001354690.2:c.1113T>C
NM_001354691.2:c.870T>C
NM_001354692.2:c.870T>C
NM_001354693.2:c.1014T>C
NM_001354694.2:c.930T>C
NM_001354695.2:c.771T>C
NR_148940.2:n.1557T>C
NR_148941.2:n.1503T>C
NR_148942.2:n.1442T>C
ENST00000251849.8:c.1113T>C
ENST00000423275.5:c.*790T>C
ENST00000432427.2:n.750T>C
ENST00000442415.6:c.1173T>C
ENST00000460610.1:n.70T>C
ENST00000465826.5:n.470T>C
ENST00000475353.1:n.281T>C
ENST00000494557.1:n.129T>C
NC_000003.12:g.12591788A>G
CM000665.2:g.12591788A>G
NC_000003.11:g.12633287A>G
CM000665.1:g.12633287A>G
NC_000003.10:g.12608287A>G
NG_007467.1:g.77392T>C

Likely Benign

• Met criteria codes: BP4 BP7

• Not Met criteria codes: BS2

Expert Panel

RASopathy VCEP

Criteria Specification Information

Evidence submitted by expert panel

RASopathy VCEP

The c.1113T>C (p.Asp371=) is present in 7/1113684 European alleles (MAF 2.88e-05, 95% CI) gnomAD v2.1.1. Sixteen apparently unaffected parental samples involved in whole exome testing were observed with this variant supporting that this variant is likely benign; however, this evidence does not meet current scoring criteria for BS2 at this time (BS2 not met; SCV000515669.4). This variant is a synonymous (silent) variant at a nucleotide that is not highly conserved and is not predicted to impact splicing (BP7). Computational prediction tools and conservation analysis suggest that the p.Asp371= variant does not impact the protein (BP4). In summary, the clinical significance of the p.Asp371= variant is likely benign. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): BP7, BP4.

Met criteria codes

• BP4: No predicted splicing impact
• BP7: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Not Met criteria codes

• BS2: Not met, 3 well-phenotyped individuals needed to apply BS2. Identified by whole exome in 16 unaffected parents from 16 different trios (SCV000515669.4) observed a female in her 20's with a history of autism, type 2 diabetes, and dilated LV heart failure (SCV001010386.1).