Variant chr20-1478599-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001122962.2(SIRPB2):c.460G>T(p.Asp154Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000477 in 1,565,442 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D154N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00048 ( 2 hom. )

Consequence

SIRPB2
NM_001122962.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.09

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04472506).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIRPB2	NM_001122962.2 linkuse as main transcript	c.460G>T	p.Asp154Tyr	missense_variant	3/5	ENST00000359801.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIRPB2	ENST00000359801.8 linkuse as main transcript	c.460G>T	p.Asp154Tyr	missense_variant	3/5	2	NM_001122962.2	P1	Q5JXA9-1

Frequencies

GnomAD3 genomes

AF:

0.000453

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

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:

0.000706

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000479

AC:

103

AN:

214944

Hom.:

AF XY:

0.000416

AC XY:

AN XY:

117866

show subpopulations

Gnomad AFR exome

AF:

0.000136

Gnomad AMR exome

AF:

0.00109

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:

0.000715

Gnomad OTH exome

AF:

0.000200

GnomAD4 exome

AF:

0.000480

AC:

678

AN:

1413130

Hom.:

Cov.:

AF XY:

0.000453

AC XY:

316

AN XY:

697000

show subpopulations

Gnomad4 AFR exome

AF:

0.000158

Gnomad4 AMR exome

AF:

0.000935

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000386

Gnomad4 NFE exome

AF:

0.000566

Gnomad4 OTH exome

AF:

0.000380

GnomAD4 genome

AF:

0.000453

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.000497

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000706

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000632

Hom.:

Bravo

AF:

0.000465

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000140

AC:

ExAC

AF:

0.000275

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

Sep 15, 2021

The c.460G>T (p.D154Y) alteration is located in exon 3 (coding exon 3) of the SIRPB2 gene. This alteration results from a G to T substitution at nucleotide position 460, causing the aspartic acid (D) at amino acid position 154 to be replaced by a tyrosine (Y). 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

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

T;.

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.096

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.045

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.4

M;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-3.6

D;D

REVEL

Benign

0.11

Sift

Uncertain

0.012

D;D

Sift4G

Uncertain

0.035

D;D

Polyphen

1.0

D;.

Vest4

0.24

MVP

0.66

MPC

0.33

ClinPred

0.073

GERP RS

2.3

Varity_R

0.20

gMVP

0.28

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