1-156815190-T-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 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: not found (cov: 33)
• Consequence: SH2D2A NM_003975.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003975.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH2D2A	NM_003975.4	MANE Select	c.155A>C	p.Asn52Thr	missense	Exon 3 of 9	NP_003966.2	Q9NP31-1
	SH2D2A	NM_001161441.2		c.155A>C	p.Asn52Thr	missense	Exon 3 of 9	NP_001154913.1	Q9NP31-2
	SH2D2A	NM_001161444.2		c.155A>C	p.Asn52Thr	missense	Exon 3 of 8	NP_001154916.1	Q9NP31-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH2D2A	ENST00000368199.8	TSL:1 MANE Select	c.155A>C	p.Asn52Thr	missense	Exon 3 of 9	ENSP00000357182.3	Q9NP31-1
	SH2D2A	ENST00000392306.2	TSL:1	c.155A>C	p.Asn52Thr	missense	Exon 3 of 9	ENSP00000376123.2	Q9NP31-2
	SH2D2A	ENST00000368198.8	TSL:1	c.101A>C	p.Asn34Thr	missense	Exon 3 of 9	ENSP00000357181.3	Q9NP31-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 48

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-1.6
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.18	N
REVEL	Benign	0.031
Sift	Benign	1.0	T
Sift4G	Benign	0.66	T
Polyphen		0.0	B
Vest4		0.16
MutPred		0.16		Gain of glycosylation at N52 (P = 0.0011)
MVP		0.36
MPC		0.26
ClinPred		0.026	T
GERP RS		-9.9
PromoterAI		0.0040	Neutral
Varity_R		0.025
gMVP		0.099
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs926103; hg19: chr1-156784982;