2-38984217-TAA-TA

Position:

• chr2-38984217-TAA-TA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_005633.4(SOS1):​c.*1606delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.93 (66417 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: SOS1 NM_005633.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.00

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]

SOS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 2-38984217-TA-T is Benign according to our data. Variant chr2-38984217-TA-T is described in ClinVar as [Likely_benign]. Clinvar id is 212288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOS1	NM_005633.4	c.*1606delT		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	c.*1606delT		3_prime_UTR_variant	23/23	1	NM_005633.4	ENSP00000384675.2

Frequencies

GnomAD3 genomes AF: 0.933 AC: 141962 AN: 152102 Hom.: 66360 Cov.: 0

Gnomad AFR AF: 0.948

Gnomad AMI AF: 0.906

Gnomad AMR AF: 0.939

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.835

Gnomad FIN AF: 0.972

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.935

Gnomad OTH AF: 0.921

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.933 AC: 142078 AN: 152220 Hom.: 66417 Cov.: 0 AF XY: 0.931 AC XY: 69303 AN XY: 74416

Gnomad4 AFR AF: 0.948

Gnomad4 AMR AF: 0.939

Gnomad4 ASJ AF: 0.908

Gnomad4 EAS AF: 0.815

Gnomad4 SAS AF: 0.836

Gnomad4 FIN AF: 0.972

Gnomad4 NFE AF: 0.935

Gnomad4 OTH AF: 0.921

Alfa AF: 0.938 Hom.: 8151

Bravo AF: 0.932

Asia WGS AF: 0.849 AC: 2952 AN: 3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 30, 2015

- -

Noonan syndrome 4 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

-

- -

Gingival fibromatosis Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Noonan syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Fibromatosis, gingival, 1 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

-

- -

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: rs34248802; hg19: chr2-39211358;