Variant 10-80603585-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001388272.1(SH2D4B):c.650G>A(p.Arg217Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000889 in 1,552,900 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 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000091 ( 0 hom. )

Consequence

SH2D4B
NM_001388272.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.92

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 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=0.1749166).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SH2D4B	NM_001388272.1 linkuse as main transcript	c.650G>A	p.Arg217Gln	missense_variant	5/8	ENST00000646907.2
SH2D4B	NM_207372.2 linkuse as main transcript	c.650G>A	p.Arg217Gln	missense_variant	5/7
SH2D4B	NM_001145719.1 linkuse as main transcript	c.503G>A	p.Arg168Gln	missense_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH2D4B	ENST00000646907.2 linkuse as main transcript	c.650G>A	p.Arg217Gln	missense_variant	5/8		NM_001388272.1	P1
SH2D4B	ENST00000339284.6 linkuse as main transcript	c.650G>A	p.Arg217Gln	missense_variant	5/7	2			Q5SQS7-2
SH2D4B	ENST00000313455.5 linkuse as main transcript	c.503G>A	p.Arg168Gln	missense_variant	5/7	2			Q5SQS7-3

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000176

AC:

AN:

164686

Hom.:

AF XY:

0.000218

AC XY:

AN XY:

87350

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000317

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000514

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000107

Gnomad OTH exome

AF:

0.000440

GnomAD4 exome

AF:

0.0000907

AC:

127

AN:

1400550

Hom.:

Cov.:

AF XY:

0.000100

AC XY:

AN XY:

690126

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000221

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000453

Gnomad4 FIN exome

AF:

0.0000202

Gnomad4 NFE exome

AF:

0.0000686

Gnomad4 OTH exome

AF:

0.000138

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152350

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000203

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000948

AC:

Asia WGS

AF:

0.00115

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

Aug 12, 2021

The c.650G>A (p.R217Q) alteration is located in exon 5 (coding exon 5) of the SH2D4B gene. This alteration results from a G to A substitution at nucleotide position 650, causing the arginine (R) at amino acid position 217 to be replaced by a glutamine (Q). 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

-0.35

BayesDel_noAF

Benign

-0.40

Cadd

Pathogenic

Dann

Pathogenic

1.0

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.9

N;.;N

REVEL

Benign

0.18

Sift

Uncertain

0.0090

D;.;D

Sift4G

Uncertain

0.018

D;.;D

Polyphen

1.0

D;.;D

Vest4

0.58

MutPred

0.17

Loss of MoRF binding (P = 0.0415);Loss of MoRF binding (P = 0.0415);.;

MVP

0.76

MPC

0.64

ClinPred

0.12

GERP RS

6.0

gMVP

0.24

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