20-1478599-C-T

Position:

• chr20-1478599-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001122962.2(SIRPB2):​c.460G>A​(p.Asp154Asn) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SIRPB2 NM_001122962.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.09

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08024672).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIRPB2	NM_001122962.2	c.460G>A	p.Asp154Asn	missense_variant	3/5	ENST00000359801.8	NP_001116434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIRPB2	ENST00000359801.8	c.460G>A	p.Asp154Asn	missense_variant	3/5	2	NM_001122962.2	ENSP00000352849	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1413132 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 697002

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 24, 2024

The c.460G>A (p.D154N) alteration is located in exon 3 (coding exon 3) of the SIRPB2 gene. This alteration results from a G to A substitution at nucleotide position 460, causing the aspartic acid (D) at amino acid position 154 to be replaced by an asparagine (N). 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	0.087
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0040	T;.
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.080	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.99	L;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.012
Sift	Benign	0.23	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.058	B;.
Vest4		0.066
MutPred		0.37		Gain of loop (P = 0.1069);.;
MVP		0.49
MPC		0.051
ClinPred		0.13	T
GERP RS		2.3
Varity_R		0.081
gMVP		0.076

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-1459244;