chr2-38982105-AC-A

Position:

• chr2-38982105-AC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000402219.8(SOS1):​c.*3718del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00703 in 152,266 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0070 (6 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: SOS1 ENST00000402219.8 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.318

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 -10 ACMG points.

• BP6: Variant 2-38982105-AC-A is Benign according to our data. Variant chr2-38982105-AC-A is described in ClinVar as [Benign]. Clinvar id is 1701378.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOS1	NM_005633.4	c.*3718del		3_prime_UTR_variant	23/23	ENST00000402219.8	NP_005624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOS1	ENST00000402219.8	c.*3718del		3_prime_UTR_variant	23/23	1	NM_005633.4	ENSP00000384675	A1
SOS1	ENST00000685279.1	c.*3718del		3_prime_UTR_variant	15/15			ENSP00000509424
SOS1	ENST00000692089.1	c.3399+5367del		intron_variant				ENSP00000508626

Frequencies

GnomAD3 genomes AF: 0.00703 AC: 1070 AN: 152142 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00220

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00636

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00339

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.00959

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

Gnomad4 AFR exome AF: 0.00

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.00702 AC: 1069 AN: 152260 Hom.: 6 Cov.: 32 AF XY: 0.00645 AC XY: 480 AN XY: 74448

Gnomad4 AFR AF: 0.00219

Gnomad4 AMR AF: 0.00635

Gnomad4 ASJ AF: 0.0248

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.00339

Gnomad4 NFE AF: 0.0106

Gnomad4 OTH AF: 0.00949

Alfa AF: 0.00848 Hom.: 0

Bravo AF: 0.00740

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

SOS1: BS1, BS2 -

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: rs367976289; hg19: chr2-39209246;