chr3-184234751-G-A

Position:

• chr3-184234751-G-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.941G>A​(p.Arg314Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000838 in 1,550,536 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R314W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000075 (0 hom.)
• Consequence: VWA5B2 NM_001390846.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49

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=0.052801877).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VWA5B2	NM_001390846.1	c.941G>A	p.Arg314Gln	missense_variant	7/20	ENST00000691901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VWA5B2	ENST00000691901.1	c.941G>A	p.Arg314Gln	missense_variant	7/20		NM_001390846.1	P1

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152212 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000586 AC: 9 AN: 153546 Hom.: 0 AF XY: 0.0000367 AC XY: 3 AN XY: 81836

Gnomad AFR exome AF: 0.000138

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000119

Gnomad NFE exome AF: 0.000103

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000751 AC: 105 AN: 1398206 Hom.: 0 Cov.: 32 AF XY: 0.0000667 AC XY: 46 AN XY: 689634

Gnomad4 AFR exome AF: 0.0000633

Gnomad4 AMR exome AF: 0.0000280

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000114

Gnomad4 FIN exome AF: 0.000124

Gnomad4 NFE exome AF: 0.0000742

Gnomad4 OTH exome AF: 0.000121

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152330 Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14 AN XY: 74498

Gnomad4 AFR AF: 0.000192

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000959 Hom.: 0

Bravo AF: 0.000117

ExAC AF: 0.0000449 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.096	.;T
Eigen	Benign	-0.032
Eigen_PC	Benign	0.070
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.053	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.051
Sift	Uncertain	0.022	D;D
Sift4G	Uncertain	0.012	D;D
Polyphen		0.13	.;B
Vest4		0.12
MVP		0.092
MPC		0.73
ClinPred		0.17	T
GERP RS		4.0
Varity_R		0.39
gMVP		0.41

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

LitVar

Other links and lift over

dbSNP: rs752607575; hg19: chr3-183952539; COSMIC: COSV56610937; COSMIC: COSV56610937;