chr16-28866144-C-G

Variant names:

• chr16-28866144-C-G
• NM_001387430.1:c.50C>G

Variant summary

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

The NM_001387430.1(SH2B1):​c.50C>G​(p.Pro17Arg) 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. 12/21 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: SH2B1 NM_001387430.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.45

Genes affected

SH2B1 (HGNC:30417): (SH2B adaptor protein 1) This gene encodes a member of the SH2-domain containing mediators family. The encoded protein mediates activation of various kinases and may function in cytokine and growth factor receptor signaling and cellular transformation. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2009]

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=0.12552816).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH2B1	NM_001387430.1	c.50C>G	p.Pro17Arg	missense_variant	Exon 1 of 8	ENST00000684370.1	NP_001374359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH2B1	ENST00000684370.1	c.50C>G	p.Pro17Arg	missense_variant	Exon 1 of 8		NM_001387430.1	ENSP00000507475.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T;T;.;T;T;.;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.67	T;.;.;T;T;T;T
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.13	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	.;L;L;.;L;L;L
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.2	N;N;N;N;.;N;N
REVEL	Benign	0.055
Sift	Benign	0.059	T;D;D;D;.;D;D
Sift4G	Uncertain	0.033	D;D;D;D;D;D;D
Polyphen		0.62, 0.27	.;P;B;.;P;B;B
Vest4		0.37, 0.27, 0.36, 0.34, 0.35
MutPred		0.20		Loss of glycosylation at P17 (P = 0.0025);Loss of glycosylation at P17 (P = 0.0025);Loss of glycosylation at P17 (P = 0.0025);Loss of glycosylation at P17 (P = 0.0025);Loss of glycosylation at P17 (P = 0.0025);Loss of glycosylation at P17 (P = 0.0025);Loss of glycosylation at P17 (P = 0.0025);
MVP		0.068
MPC		0.45
ClinPred		0.74	D
GERP RS		2.7
Varity_R		0.038
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr16-28877465;