16-28866160-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001387430.1(SH2B1):c.66G>C(p.Pro22=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P22P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000017 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0022 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SH2B1 NM_001387430.1 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.206

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 16-28866160-G-C is Benign according to our data. Variant chr16-28866160-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 765123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.206 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH2B1	NM_001387430.1	c.66G>C	p.Pro22=	synonymous_variant	1/8	ENST00000684370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH2B1	ENST00000684370.1	c.66G>C	p.Pro22=	synonymous_variant	1/8		NM_001387430.1	P3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 2 AN: 115410 Hom.: 0 Cov.: 30 FAILED QC

Gnomad AFR AF: 0.0000318

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000149

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00219 AC: 1689 AN: 772810 Hom.: 0 Cov.: 35 AF XY: 0.00228 AC XY: 875 AN XY: 383662

Gnomad4 AFR exome AF: 0.00115

Gnomad4 AMR exome AF: 0.00427

Gnomad4 ASJ exome AF: 0.00461

Gnomad4 EAS exome AF: 0.00377

Gnomad4 SAS exome AF: 0.00469

Gnomad4 FIN exome AF: 0.00514

Gnomad4 NFE exome AF: 0.00170

Gnomad4 OTH exome AF: 0.00360

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000173 AC: 2 AN: 115464 Hom.: 0 Cov.: 30 AF XY: 0.0000353 AC XY: 2 AN XY: 56654

Gnomad4 AFR AF: 0.0000318

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000149

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

SH2B1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 04, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	6.4
Dann	Benign	0.81

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

Publications

LitVar

Other links and lift over

dbSNP: rs945365382; hg19: chr16-28877481;