chr3-184233388-G-T

Position:

• chr3-184233388-G-T

Variant summary

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

The NM_001390846.1(VWA5B2):​c.521G>T​(p.Cys174Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,383,026 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: VWA5B2 NM_001390846.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.96

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VWA5B2	NM_001390846.1	c.521G>T	p.Cys174Phe	missense_variant	4/20	ENST00000691901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VWA5B2	ENST00000691901.1	c.521G>T	p.Cys174Phe	missense_variant	4/20		NM_001390846.1	P1
VWA5B2	ENST00000426955.6	c.521G>T	p.Cys174Phe	missense_variant	3/19	1		P1
VWA5B2	ENST00000497229.1	n.789G>T		non_coding_transcript_exon_variant	1/3	2
VWA5B2	ENST00000273794.5			upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000434 AC: 6 AN: 1383026 Hom.: 0 Cov.: 33 AF XY: 0.00000293 AC XY: 2 AN XY: 681580

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: 0.00000559

Gnomad4 OTH exome AF: 0.00

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

Jul 06, 2021

The c.521G>T (p.C174F) alteration is located in exon 3 (coding exon 3) of the VWA5B2 gene. This alteration results from a G to T substitution at nucleotide position 521, causing the cysteine (C) at amino acid position 174 to be replaced by a phenylalanine (F). 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	Uncertain	0.40
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	28
DANN	Benign	0.96
DEOGEN2	Benign	0.014	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.14
Sift	Benign	0.34	T
Sift4G	Uncertain	0.044	D
Vest4		0.65
MutPred		0.21		Gain of glycosylation at S177 (P = 0.1202);
MVP		0.54
MPC		1.6
ClinPred		0.86	D
GERP RS		4.2
Varity_R		0.34
gMVP		0.72

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: chr3-183951176;