Variant 10-80570283-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001388272.1(SH2D4B):c.314G>A(p.Arg105Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000713 in 1,613,516 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 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

SH2D4B
NM_001388272.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.85

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3131235).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SH2D4B	NM_001388272.1 linkuse as main transcript	c.314G>A	p.Arg105Gln	missense_variant	2/8	ENST00000646907.2	NP_001375201.1
SH2D4B	NM_207372.2 linkuse as main transcript	c.314G>A	p.Arg105Gln	missense_variant	2/7		NP_997255.2
SH2D4B	NM_001145719.1 linkuse as main transcript	c.167G>A	p.Arg56Gln	missense_variant	2/7		NP_001139191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH2D4B	ENST00000646907.2 linkuse as main transcript	c.314G>A	p.Arg105Gln	missense_variant	2/8		NM_001388272.1	ENSP00000494732	P1
SH2D4B	ENST00000339284.6 linkuse as main transcript	c.314G>A	p.Arg105Gln	missense_variant	2/7	2		ENSP00000345295		Q5SQS7-2
SH2D4B	ENST00000313455.5 linkuse as main transcript	c.167G>A	p.Arg56Gln	missense_variant	2/7	2		ENSP00000314242		Q5SQS7-3

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152172

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000637

AC:

AN:

251356

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000732

AC:

107

AN:

1461344

Hom.:

Cov.:

AF XY:

0.0000743

AC XY:

AN XY:

726958

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000899

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000254

Hom.:

Bravo

AF:

0.0000642

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000119

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

Apr 26, 2024

The c.314G>A (p.R105Q) alteration is located in exon 2 (coding exon 2) of the SH2D4B gene. This alteration results from a G to A substitution at nucleotide position 314, causing the arginine (R) at amino acid position 105 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

-0.14

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Pathogenic

1.0

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.31

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.9

N;.;N

REVEL

Benign

0.21

Sift

Benign

0.092

T;.;T

Sift4G

Benign

0.080

T;.;T

Polyphen

1.0

D;.;D

Vest4

0.55

MVP

0.74

MPC

0.67

ClinPred

0.43

GERP RS

5.6

gMVP

0.58

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