rs199625818

Variant names:

• chr20-1476319-C-A
• rs199625818
• NM_001122962.2:c.877G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-1476319-C-A
• chr20-1476319-C-G
• chr20-1476319-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001122962.2(SIRPB2):​c.877G>T​(p.Ala293Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A293T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SIRPB2 NM_001122962.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750

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]

ACMG classification

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=0.049014658).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRPB2	NM_001122962.2	c.877G>T	p.Ala293Ser	missense_variant	Exon 5 of 5	ENST00000359801.8	NP_001116434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRPB2	ENST00000359801.8	c.877G>T	p.Ala293Ser	missense_variant	Exon 5 of 5	2	NM_001122962.2	ENSP00000352849.3
SIRPB2	ENST00000444444.2	c.583G>T	p.Ala195Ser	missense_variant	Exon 5 of 5	2		ENSP00000402438.1
SIRPB2	ENST00000481731.5	n.859+1019G>T		intron_variant	Intron 4 of 7	5		ENSP00000432656.1
SIRPB2	ENST00000486775.5	n.859+1019G>T		intron_variant	Intron 4 of 6	5		ENSP00000435045.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.80
DANN	Benign	0.76
DEOGEN2	Benign	0.0016	T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0071	N
LIST_S2	Benign	0.39	T;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.049	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.34	N;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.15	N;N
REVEL	Benign	0.027
Sift	Benign	0.43	T;T
Sift4G	Benign	0.13	T;T
Polyphen		0.020	B;.
Vest4		0.062
MutPred		0.51		Gain of glycosylation at A293 (P = 0.0429);.;
MVP		0.13
MPC		0.048
ClinPred		0.045	T
GERP RS		-5.6
Varity_R		0.041
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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

Other links and lift over

dbSNP: rs199625818; hg19: chr20-1456964;