Variant chr15-78094198-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001101404.2(SH2D7):c.263A>G(p.Tyr88Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000249 in 1,607,530 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

SH2D7
NM_001101404.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.87

Variant links:

Genes affected

SH2D7 (HGNC:34549): (SH2 domain containing 7)

SH2D7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH2D7	NM_001101404.2 linkuse as main transcript	c.263A>G	p.Tyr88Cys	missense_variant	2/6	ENST00000328828.6	NP_001094874.1	A6NKC9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SH2D7	ENST00000328828.6 linkuse as main transcript	c.263A>G	p.Tyr88Cys	missense_variant	2/6	5	NM_001101404.2	ENSP00000327846.5	A6NKC9
SH2D7	ENST00000409568.6 linkuse as main transcript	c.-146A>G		5_prime_UTR_premature_start_codon_gain_variant	2/6	5		ENSP00000386676.2	B8ZZB5
SH2D7	ENST00000409568.6 linkuse as main transcript	c.-146A>G		5_prime_UTR_variant	2/6	5		ENSP00000386676.2	B8ZZB5

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000960

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000891

AC:

AN:

235764

Hom.:

AF XY:

0.0000862

AC XY:

AN XY:

127594

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00123

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000241

AC:

AN:

1455172

Hom.:

Cov.:

AF XY:

0.0000235

AC XY:

AN XY:

723072

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000886

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152358

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000963

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000771

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.000107

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 26, 2024

The c.263A>G (p.Y88C) alteration is located in exon 2 (coding exon 2) of the SH2D7 gene. This alteration results from a A to G substitution at nucleotide position 263, causing the tyrosine (Y) at amino acid position 88 to be replaced by a cysteine (C). 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

Pathogenic

0.65

BayesDel_addAF

Benign

-0.046

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.68

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.28

MetaRNN

Uncertain

0.46

MetaSVM

Uncertain

-0.022

MutationAssessor

Uncertain

2.7

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-8.1

REVEL

Pathogenic

0.68

Sift

Uncertain

0.0060

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.76

MVP

0.89

MPC

0.30

ClinPred

0.85

GERP RS

4.4

Varity_R

0.66

gMVP

0.79

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over