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. The variant received -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. 16/22 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
• Publications: 3 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049014658).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122962.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRPB2	NM_001122962.2	MANE Select	c.877G>T	p.Ala293Ser	missense	Exon 5 of 5	NP_001116434.1	Q5JXA9-1
	SIRPB2	NM_001134836.2		c.583G>T	p.Ala195Ser	missense	Exon 5 of 5	NP_001128308.1	Q5JXA9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRPB2	ENST00000359801.8	TSL:2 MANE Select	c.877G>T	p.Ala293Ser	missense	Exon 5 of 5	ENSP00000352849.3	Q5JXA9-1
	SIRPB2	ENST00000444444.2	TSL:2	c.583G>T	p.Ala195Ser	missense	Exon 5 of 5	ENSP00000402438.1	Q5JXA9-3
	SIRPB2	ENST00000965661.1		c.535G>T	p.Ala179Ser	missense	Exon 4 of 4	ENSP00000635720.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 247374 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.075
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.027
Sift	Benign	0.43	T
Sift4G	Benign	0.13	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
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs199625818; hg19: chr20-1456964;