rs375759094

Variant names:

• chr20-1478493-C-A
• NM_001122962.2:c.566G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-1478493-C-A
• chr20-1478493-C-G
• chr20-1478493-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001122962.2(SIRPB2):​c.566G>T​(p.Gly189Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. G189E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SIRPB2 NM_001122962.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.63

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.891

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRPB2	NM_001122962.2	c.566G>T	p.Gly189Val	missense_variant	Exon 3 of 5	ENST00000359801.8	NP_001116434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRPB2	ENST00000359801.8	c.566G>T	p.Gly189Val	missense_variant	Exon 3 of 5	2	NM_001122962.2	ENSP00000352849.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461838 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 727222

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.078	T;.
Eigen	Uncertain	0.33
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.0085	T
MetaRNN	Pathogenic	0.89	D;D
MetaSVM	Benign	-0.82	T
MutationAssessor	Pathogenic	3.5	H;.
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-8.5	D;D
REVEL	Benign	0.26
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		1.0	D;.
Vest4		0.65
MutPred		0.73		Loss of catalytic residue at G189 (P = 0.0448);.;
MVP		0.50
MPC		0.35
ClinPred		0.92	D
GERP RS		4.0
Varity_R		0.79
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-1459138;