1-156815190-T-C

Variant names:

• chr1-156815190-T-C
• rs926103
• NM_003975.4:c.155A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003975.4(SH2D2A):​c.155A>G​(p.Asn52Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 1,583,494 control chromosomes in the GnomAD database, including 328,186 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.58 (26842 hom., cov: 33)
  • Exomes 𝑓: 0.65 (301344 hom.)
• Consequence: SH2D2A NM_003975.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0207865E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH2D2A	NM_003975.4	c.155A>G	p.Asn52Ser	missense_variant	Exon 3 of 9	ENST00000368199.8	NP_003966.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH2D2A	ENST00000368199.8	c.155A>G	p.Asn52Ser	missense_variant	Exon 3 of 9	1	NM_003975.4	ENSP00000357182.3

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88209 AN: 151996 Hom.: 26825 Cov.: 33

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.823

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.645

Gnomad OTH AF: 0.597

GnomAD3 exomes AF: 0.643 AC: 139350 AN: 216768 Hom.: 45352 AF XY: 0.647 AC XY: 75667 AN XY: 116958

Gnomad AFR exome AF: 0.375

Gnomad AMR exome AF: 0.676

Gnomad ASJ exome AF: 0.604

Gnomad EAS exome AF: 0.821

Gnomad SAS exome AF: 0.656

Gnomad FIN exome AF: 0.637

Gnomad NFE exome AF: 0.642

Gnomad OTH exome AF: 0.640

GnomAD4 exome AF: 0.646 AC: 924923 AN: 1431380 Hom.: 301344 Cov.: 48 AF XY: 0.647 AC XY: 459788 AN XY: 710194

Gnomad4 AFR exome AF: 0.362

Gnomad4 AMR exome AF: 0.671

Gnomad4 ASJ exome AF: 0.591

Gnomad4 EAS exome AF: 0.819

Gnomad4 SAS exome AF: 0.656

Gnomad4 FIN exome AF: 0.632

Gnomad4 NFE exome AF: 0.649

Gnomad4 OTH exome AF: 0.642

GnomAD4 genome AF: 0.580 AC: 88264 AN: 152114 Hom.: 26842 Cov.: 33 AF XY: 0.587 AC XY: 43622 AN XY: 74372

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.585

Gnomad4 EAS AF: 0.822

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.648

Gnomad4 NFE AF: 0.645

Gnomad4 OTH AF: 0.595

Alfa AF: 0.618 Hom.: 23182

Bravo AF: 0.575

TwinsUK AF: 0.640 AC: 2374

ALSPAC AF: 0.655 AC: 2526

ESP6500AA AF: 0.383 AC: 1686

ESP6500EA AF: 0.640 AC: 5505

ExAC AF: 0.621 AC: 75055

Asia WGS AF: 0.693 AC: 2409 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.0090
DANN	Benign	0.28
DEOGEN2	Benign	0.23	.;T;.
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.0042	N
LIST_S2	Benign	0.22	T;T;T
MetaRNN	Benign	0.0000010	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.11	.;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.070	N;N;N
REVEL	Benign	0.035
Sift	Benign	0.71	T;T;T
Sift4G	Benign	0.82	T;T;T
Polyphen		0.0	.;B;B
Vest4		0.020
MPC		0.20
ClinPred		0.019	T
GERP RS		-9.9
Varity_R		0.012
gMVP		0.075

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: rs926103; hg19: chr1-156784982;