2-98229630-A-G

Position:

• chr2-98229630-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144992.5(VWA3B):​c.2151-420A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.898 in 152,276 control chromosomes in the GnomAD database, including 61,656 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.90 (61656 hom., cov: 32)
• Consequence: VWA3B NM_144992.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

Genes affected

VWA3B (HGNC:28385): (von Willebrand factor A domain containing 3B) This gene encodes an intracellular protein that contains a von Willebrand factor type A domain. Intracellular proteins with VWA domains are thought to function in transcription, DNA repair, ribosomal and membrane transport and the proteasome. Mutations in this gene are associated with Spinocerebellar ataxia, autosomal recessive 22. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, May 2017]

VWA3B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWA3B	NM_144992.5	c.2151-420A>G		intron_variant		ENST00000477737.6	NP_659429.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWA3B	ENST00000477737.6	c.2151-420A>G		intron_variant		1	NM_144992.5	ENSP00000417955.1

Frequencies

GnomAD3 genomes AF: 0.898 AC: 136598 AN: 152158 Hom.: 61599 Cov.: 32

Gnomad AFR AF: 0.971

Gnomad AMI AF: 0.909

Gnomad AMR AF: 0.887

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.956

Gnomad FIN AF: 0.919

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.867

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.898 AC: 136714 AN: 152276 Hom.: 61656 Cov.: 32 AF XY: 0.902 AC XY: 67126 AN XY: 74454

Gnomad4 AFR AF: 0.971

Gnomad4 AMR AF: 0.887

Gnomad4 ASJ AF: 0.851

Gnomad4 EAS AF: 0.974

Gnomad4 SAS AF: 0.956

Gnomad4 FIN AF: 0.919

Gnomad4 NFE AF: 0.845

Gnomad4 OTH AF: 0.869

Alfa AF: 0.876 Hom.: 9876

Bravo AF: 0.897

Asia WGS AF: 0.957 AC: 3328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.7
DANN	Benign	0.69

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: rs12052316; hg19: chr2-98846093;