chr2-38983578-T-TTA

Position:

• chr2-38983578-T-TTA

Variant summary

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

The NM_005633.4(SOS1):​c.*2244_*2245dupTA 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 0.80 (50972 hom., cov: 0)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: SOS1 NM_005633.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.633

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 -16 ACMG points.

• BP6: Variant 2-38983578-T-TTA is Benign according to our data. Variant chr2-38983578-T-TTA is described in ClinVar as [Likely_benign]. Clinvar id is 212289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOS1	NM_005633.4	c.*2244_*2245dupTA		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.*2244_*2245dupTA		3_prime_UTR_variant	23/23	1	NM_005633.4	ENSP00000384675.2
SOS1	ENST00000685279	c.*2244_*2245dupTA		3_prime_UTR_variant	15/15			ENSP00000509424.1
SOS1	ENST00000692089.1	c.3399+3893_3399+3894dupTA		intron_variant				ENSP00000508626.1

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121089 AN: 151862 Hom.: 50955 Cov.: 0

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.906

Gnomad AMR AF: 0.879

Gnomad ASJ AF: 0.879

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.968

Gnomad MID AF: 0.855

Gnomad NFE AF: 0.923

Gnomad OTH AF: 0.822

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.797 AC: 121140 AN: 151980 Hom.: 50972 Cov.: 0 AF XY: 0.799 AC XY: 59366 AN XY: 74292

Gnomad4 AFR AF: 0.500

Gnomad4 AMR AF: 0.880

Gnomad4 ASJ AF: 0.879

Gnomad4 EAS AF: 0.809

Gnomad4 SAS AF: 0.828

Gnomad4 FIN AF: 0.968

Gnomad4 NFE AF: 0.923

Gnomad4 OTH AF: 0.823

Alfa AF: 0.851 Hom.: 6956

Bravo AF: 0.774

Asia WGS AF: 0.809 AC: 2814 AN: 3476

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs3832123; hg19: chr2-39210719;