rs532594344

chr2-39006537-GA-Gchr2-39006537-GA-GAAchr2-39006537-GA-GAAAAAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_005633.4(SOS1):c.2674-9del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000761 in 1,392,134 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000082 (0 hom.)
• Consequence: SOS1 NM_005633.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.647

Genes affected

SOS1 (HGNC:11187): (SOS Ras/Rac guanine nucleotide exchange factor 1) This gene encodes a protein that is a guanine nucleotide exchange factor for RAS proteins, membrane proteins that bind guanine nucleotides and participate in signal transduction pathways. GTP binding activates and GTP hydrolysis inactivates RAS proteins. The product of this gene may regulate RAS proteins by facilitating the exchange of GTP for GDP. Mutations in this gene are associated with gingival fibromatosis 1 and Noonan syndrome type 4. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP6: Variant 2-39006537-GA-G is Benign according to our data. Variant chr2-39006537-GA-G is described in ClinVar as [Likely_benign]. Clinvar id is 700501.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-39006537-GA-G is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOS1	NM_005633.4	c.2674-9del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000402219.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOS1	ENST00000402219.8	c.2674-9del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_005633.4	A1

Frequencies

GnomAD3 genomes AF: 0.0000264 AC: 4 AN: 151376 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000822 AC: 102 AN: 1240640 Hom.: 0 Cov.: 18 AF XY: 0.0000796 AC XY: 50 AN XY: 628384

Gnomad4 AFR exome AF: 0.000103

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000406

Gnomad4 EAS exome AF: 0.000260

Gnomad4 SAS exome AF: 0.0000740

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.0000833

Gnomad4 OTH exome AF: 0.0000754

GnomAD4 genome AF: 0.0000264 AC: 4 AN: 151494 Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2 AN XY: 74012

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000264

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Noonan syndrome 4 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

-

- -

Fibromatosis, gingival, 1 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

-

- -

Noonan syndrome and Noonan-related syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jul 01, 2018

- -

RASopathy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Oct 03, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs532594344; hg19: chr2-39233678;