1-156815190-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000368199.8(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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.58 (26842 hom., cov: 33)
  • Exomes 𝑓: 0.65 (301344 hom.)
• Consequence: SH2D2A ENST00000368199.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 41 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000368199.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH2D2A	NM_003975.4	MANE Select	c.155A>G	p.Asn52Ser	missense	Exon 3 of 9	NP_003966.2
	SH2D2A	NM_001161441.2		c.155A>G	p.Asn52Ser	missense	Exon 3 of 9	NP_001154913.1
	SH2D2A	NM_001161444.2		c.155A>G	p.Asn52Ser	missense	Exon 3 of 8	NP_001154916.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH2D2A	ENST00000368199.8	TSL:1 MANE Select	c.155A>G	p.Asn52Ser	missense	Exon 3 of 9	ENSP00000357182.3
	SH2D2A	ENST00000392306.2	TSL:1	c.155A>G	p.Asn52Ser	missense	Exon 3 of 9	ENSP00000376123.2
	SH2D2A	ENST00000368198.8	TSL:1	c.101A>G	p.Asn34Ser	missense	Exon 3 of 9	ENSP00000357181.3

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

GnomAD2 exomes AF: 0.643 AC: 139350 AN: 216768 AF XY: 0.647

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 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

African (AFR) AF: 0.362 AC: 11778 AN: 32556

American (AMR) AF: 0.671 AC: 27377 AN: 40826

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 14509 AN: 24564

East Asian (EAS) AF: 0.819 AC: 31509 AN: 38476

South Asian (SAS) AF: 0.656 AC: 53902 AN: 82174

European-Finnish (FIN) AF: 0.632 AC: 33051 AN: 52256

Middle Eastern (MID) AF: 0.645 AC: 3616 AN: 5608

European-Non Finnish (NFE) AF: 0.649 AC: 711300 AN: 1095936

Other (OTH) AF: 0.642 AC: 37881 AN: 58984

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

African (AFR) AF: 0.387 AC: 16041 AN: 41488

American (AMR) AF: 0.653 AC: 9995 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2028 AN: 3468

East Asian (EAS) AF: 0.822 AC: 4252 AN: 5170

South Asian (SAS) AF: 0.650 AC: 3133 AN: 4822

European-Finnish (FIN) AF: 0.648 AC: 6869 AN: 10606

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.645 AC: 43791 AN: 67944

Other (OTH) AF: 0.595 AC: 1257 AN: 2112

Alfa AF: 0.616 Hom.: 25377

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 v4.9

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
MetaRNN	Benign	0.0000010	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.11	N
PhyloP100		-1.6
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.035
Sift	Benign	0.71	T
Sift4G	Benign	0.82	T
Polyphen		0.0	B
Vest4		0.020
MPC		0.20
ClinPred		0.019	T
GERP RS		-9.9
PromoterAI		0.011	Neutral
Varity_R		0.012
gMVP		0.075
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs926103; hg19: chr1-156784982; COSMIC: COSV107464830; COSMIC: COSV107464830;