Variant 15-78094141-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001101404.2(SH2D7):c.206C>T(p.Ala69Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000157 in 1,609,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

SH2D7
NM_001101404.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.894

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02152273).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH2D7	NM_001101404.2 linkuse as main transcript	c.206C>T	p.Ala69Val	missense_variant	2/6	ENST00000328828.6	NP_001094874.1	A6NKC9
SH2D7	XM_017022487.2 linkuse as main transcript	c.91C>T	p.Leu31Phe	missense_variant	2/7		XP_016877976.2
SH2D7	XM_047432942.1 linkuse as main transcript	c.49C>T	p.Leu17Phe	missense_variant	2/7		XP_047288898.1
SH2D7	XM_047432944.1 linkuse as main transcript	c.-386C>T		5_prime_UTR_variant	1/4		XP_047288900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH2D7	ENST00000328828.6 linkuse as main transcript	c.206C>T	p.Ala69Val	missense_variant	2/6	5	NM_001101404.2	ENSP00000327846.5		A6NKC9
SH2D7	ENST00000409568.6 linkuse as main transcript	c.-203C>T		5_prime_UTR_variant	2/6	5		ENSP00000386676.2		B8ZZB5

Frequencies

GnomAD3 genomes

AF:

0.000144

AC:

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000217

AC:

AN:

239174

Hom.:

AF XY:

0.000216

AC XY:

AN XY:

129778

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000149

Gnomad ASJ exome

AF:

0.00324

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000924

Gnomad OTH exome

AF:

0.000858

GnomAD4 exome

AF:

0.000158

AC:

230

AN:

1456888

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

117

AN XY:

724192

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00338

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000106

Gnomad4 OTH exome

AF:

0.000299

GnomAD4 genome

AF:

0.000144

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000379

Hom.:

Bravo

AF:

0.000125

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000119

AC:

ExAC

AF:

0.000140

AC:

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

Oct 06, 2021

The c.206C>T (p.A69V) alteration is located in exon 2 (coding exon 2) of the SH2D7 gene. This alteration results from a C to T substitution at nucleotide position 206, causing the alanine (A) at amino acid position 69 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

0.16

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

Eigen

Benign

0.18

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.29

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.014

MetaRNN

Benign

0.022

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.74

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.5

REVEL

Benign

0.15

Sift

Benign

0.036

Sift4G

Benign

0.16

Polyphen

0.99

Vest4

0.31

MVP

0.53

MPC

0.25

ClinPred

0.10

GERP RS

5.6

Varity_R

0.21

gMVP

0.29

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