Variant chr10-80588639-G-A 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_001388272.1(SH2D4B):c.505G>A(p.Glu169Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000463 in 1,613,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00049 ( 0 hom. )

Consequence

SH2D4B
NM_001388272.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.62

Variant links:

Genes affected

SH2D4B (HGNC:31440): (SH2 domain containing 4B) Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SH2D4B 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=0.058475792).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SH2D4B	NM_001388272.1 linkuse as main transcript	c.505G>A	p.Glu169Lys	missense_variant	4/8	ENST00000646907.2	NP_001375201.1
SH2D4B	NM_207372.2 linkuse as main transcript	c.505G>A	p.Glu169Lys	missense_variant	4/7		NP_997255.2
SH2D4B	NM_001145719.1 linkuse as main transcript	c.358G>A	p.Glu120Lys	missense_variant	4/7		NP_001139191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH2D4B	ENST00000646907.2 linkuse as main transcript	c.505G>A	p.Glu169Lys	missense_variant	4/8		NM_001388272.1	ENSP00000494732	P1
SH2D4B	ENST00000339284.6 linkuse as main transcript	c.505G>A	p.Glu169Lys	missense_variant	4/7	2		ENSP00000345295		Q5SQS7-2
SH2D4B	ENST00000313455.5 linkuse as main transcript	c.358G>A	p.Glu120Lys	missense_variant	4/7	2		ENSP00000314242		Q5SQS7-3

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

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:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000378

AC:

AN:

251058

Hom.:

AF XY:

0.000383

AC XY:

AN XY:

135684

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.000141

Gnomad NFE exome

AF:

0.000756

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000489

AC:

715

AN:

1461596

Hom.:

Cov.:

AF XY:

0.000472

AC XY:

343

AN XY:

727084

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000282

Gnomad4 NFE exome

AF:

0.000607

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.000217

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000428

Hom.:

Bravo

AF:

0.000215

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000560

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000474

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

Feb 11, 2022

The c.505G>A (p.E169K) alteration is located in exon 4 (coding exon 4) of the SH2D4B gene. This alteration results from a G to A substitution at nucleotide position 505, causing the glutamic acid (E) at amino acid position 169 to be replaced by a lysine (K). 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

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.0050

MetaRNN

Benign

0.058

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.98

D;D;D;D

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.6

N;.;N

REVEL

Benign

0.20

Sift

Benign

0.16

T;.;T

Sift4G

Benign

0.19

T;.;T

Polyphen

1.0

D;.;D

Vest4

0.50

MVP

0.66

MPC

0.18

ClinPred

0.14

GERP RS

4.2

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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