chr1-156815190-T-G

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003975.4(SH2D2A):​c.155A>C​(p.Asn52Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N52S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04053867).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH2D2A	NM_003975.4	c.155A>C	p.Asn52Thr	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>C	p.Asn52Thr	missense_variant	Exon 3 of 9	1	NM_003975.4	ENSP00000357182.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 48

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.030
DANN	Benign	0.34
DEOGEN2	Benign	0.24	.;T;.
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.16	T;T;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.041	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	.;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.18	N;N;N
REVEL	Benign	0.031
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.66	T;T;T
Polyphen		0.0, 0.0010	.;B;B
Vest4		0.16
MutPred		0.16		.;Gain of glycosylation at N52 (P = 0.0011);Gain of glycosylation at N52 (P = 0.0011);
MVP		0.36
MPC		0.26
ClinPred		0.026	T
GERP RS		-9.9
Varity_R		0.025
gMVP		0.099

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-156784982;