3-184234310-C-A

Variant summary

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

The NM_001390846.1(VWA5B2):c.733C>A(p.His245Asn) 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: VWA5B2 NM_001390846.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.44

Genes affected

VWA5B2 (HGNC:25144): (von Willebrand factor A domain containing 5B2)

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=0.05058229).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VWA5B2	NM_001390846.1	c.733C>A	p.His245Asn	missense_variant	6/20	ENST00000691901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VWA5B2	ENST00000691901.1	c.733C>A	p.His245Asn	missense_variant	6/20		NM_001390846.1	P1
VWA5B2	ENST00000426955.6	c.733C>A	p.His245Asn	missense_variant	5/19	1		P1
VWA5B2	ENST00000273794.5	c.76C>A	p.His26Asn	missense_variant	3/17	2
VWA5B2	ENST00000497229.1	n.1179C>A		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Sep 01, 2021

The c.733C>A (p.H245N) alteration is located in exon 5 (coding exon 5) of the VWA5B2 gene. This alteration results from a C to A substitution at nucleotide position 733, causing the histidine (H) at amino acid position 245 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	0.11
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
Cadd	Benign	21
Dann	Uncertain	0.98
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.051	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.66	N;N;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.73	N;N
REVEL	Benign	0.027
Sift	Benign	0.30	T;T
Sift4G	Benign	0.41	T;T
Polyphen		0.035	.;B
Vest4		0.21
MutPred		0.18		.;Loss of glycosylation at P25 (P = 0.0454);
MVP		0.061
MPC		1.1
ClinPred		0.22	T
GERP RS		3.9
Varity_R		0.093
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr3-183952098;