1-156815564-T-C

Position:

• chr1-156815564-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003975.4(SH2D2A):​c.124-343A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 609,098 control chromosomes in the GnomAD database, including 250,060 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.86 (56527 hom., cov: 31)
  • Exomes 𝑓: 0.92 (193533 hom.)
• Consequence: SH2D2A NM_003975.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.71

Genes affected

SH2D2A (HGNC:10821): (SH2 domain containing 2A) This gene encodes an adaptor protein thought to function in T-cell signal transduction. A related protein in mouse is responsible for the activation of lymphocyte-specific protein-tyrosine kinase and functions in downstream signaling. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-156815564-T-C is Benign according to our data. Variant chr1-156815564-T-C is described in ClinVar as [Benign]. Clinvar id is 667736.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH2D2A	NM_003975.4	c.124-343A>G		intron_variant		ENST00000368199.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH2D2A	ENST00000368199.8	c.124-343A>G		intron_variant		1	NM_003975.4	P2
SH2D2A	ENST00000368198.7	c.70-343A>G		intron_variant		1		A2
SH2D2A	ENST00000392306.2	c.124-343A>G		intron_variant		1
SH2D2A	ENST00000495306.1	n.176-343A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.855 AC: 129925 AN: 151934 Hom.: 56484 Cov.: 31

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.971

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.881

Gnomad EAS AF: 0.936

Gnomad SAS AF: 0.896

Gnomad FIN AF: 0.898

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.942

Gnomad OTH AF: 0.872

GnomAD4 exome AF: 0.919 AC: 419804 AN: 457048 Hom.: 193533 Cov.: 3 AF XY: 0.919 AC XY: 221626 AN XY: 241210

Gnomad4 AFR exome AF: 0.682

Gnomad4 AMR exome AF: 0.829

Gnomad4 ASJ exome AF: 0.880

Gnomad4 EAS exome AF: 0.947

Gnomad4 SAS exome AF: 0.899

Gnomad4 FIN exome AF: 0.905

Gnomad4 NFE exome AF: 0.942

Gnomad4 OTH exome AF: 0.908

GnomAD4 genome AF: 0.855 AC: 130024 AN: 152050 Hom.: 56527 Cov.: 31 AF XY: 0.856 AC XY: 63640 AN XY: 74332

Gnomad4 AFR AF: 0.679

Gnomad4 AMR AF: 0.863

Gnomad4 ASJ AF: 0.881

Gnomad4 EAS AF: 0.936

Gnomad4 SAS AF: 0.897

Gnomad4 FIN AF: 0.898

Gnomad4 NFE AF: 0.942

Gnomad4 OTH AF: 0.872

Alfa AF: 0.913 Hom.: 64431

Bravo AF: 0.843

Asia WGS AF: 0.893 AC: 3106 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

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.041
DANN	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs2150906; hg19: chr1-156785356; COSMIC: COSV63885550; COSMIC: COSV63885550;