1-162402744-T-C

Position:

• chr1-162402744-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_053282.5(SH2D1B):​c.193A>G​(p.Ile65Val) 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SH2D1B NM_053282.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.62

Genes affected

SH2D1B (HGNC:30416): (SH2 domain containing 1B) By binding phosphotyrosines through its free SRC (MIM 190090) homology-2 (SH2) domain, EAT2 regulates signal transduction through receptors expressed on the surface of antigen-presenting cells (Morra et al., 2001 [PubMed 11689425]).[supplied by OMIM, Mar 2008]

SH2D1B (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14384642).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH2D1B	NM_053282.5	c.193A>G	p.Ile65Val	missense_variant	2/4	ENST00000367929.3	NP_444512.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH2D1B	ENST00000367929.3	c.193A>G	p.Ile65Val	missense_variant	2/4	1	NM_053282.5	ENSP00000356906.2
SH2D1B	ENST00000493550.1	n.315A>G		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 09, 2024

The c.193A>G (p.I65V) alteration is located in exon 2 (coding exon 2) of the SH2D1B gene. This alteration results from a A to G substitution at nucleotide position 193, causing the isoleucine (I) at amino acid position 65 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	17
DANN	Benign	0.91
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.6	L
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.16
Sift	Benign	0.11	T
Sift4G	Benign	0.42	T
Polyphen		0.0	B
Vest4		0.19
MutPred		0.40		Gain of disorder (P = 0.1326);
MVP		0.66
MPC		0.076
ClinPred		0.19	T
GERP RS		3.2
Varity_R		0.096
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs1029437277; hg19: chr1-162372534;