Variant 20-1480029-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001122962.2(SIRPB2):c.122T>C(p.Val41Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000343 in 1,456,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SIRPB2
NM_001122962.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.95

Variant links:

Genes affected

SIRPB2 (HGNC:16247): (signal regulatory protein beta 2) Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SIRPB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.765

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIRPB2	NM_001122962.2 linkuse as main transcript	c.122T>C	p.Val41Ala	missense_variant	2/5	ENST00000359801.8	NP_001116434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIRPB2	ENST00000359801.8 linkuse as main transcript	c.122T>C	p.Val41Ala	missense_variant	2/5	2	NM_001122962.2	ENSP00000352849	P1	Q5JXA9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000417

AC:

AN:

239968

Hom.:

AF XY:

0.00

AC XY:

AN XY:

131440

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000923

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1456850

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724602

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000831

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

Nov 03, 2022

The c.122T>C (p.V41A) alteration is located in exon 2 (coding exon 2) of the SIRPB2 gene. This alteration results from a T to C substitution at nucleotide position 122, causing the valine (V) at amino acid position 41 to be replaced by an alanine (A). 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

0.29

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.016

T;.

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.54

T;T

M_CAP

Benign

0.054

MetaRNN

Pathogenic

0.77

D;D

MetaSVM

Uncertain

-0.19

MutationAssessor

Pathogenic

3.3

M;M

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.2

D;N

REVEL

Benign

0.22

Sift

Uncertain

0.0020

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.99

D;.

Vest4

0.46

MutPred

0.81

Gain of disorder (P = 0.0435);Gain of disorder (P = 0.0435);

MVP

0.80

MPC

0.34

ClinPred

0.75

GERP RS

3.6

Varity_R

0.41

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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