2-98229630-A-G

Variant names:

• chr2-98229630-A-G
• rs12052316
• NM_144992.5:c.2151-420A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia, autosomal recessive 22

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
VWA3B	NM_144992.5	c.2151-420A>G		intron_variant	Intron 15 of 27	ENST00000477737.6	NP_659429.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWA3B	ENST00000477737.6	c.2151-420A>G		intron_variant	Intron 15 of 27	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

African (AFR) AF: 0.971 AC: 40359 AN: 41564

American (AMR) AF: 0.887 AC: 13576 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 2953 AN: 3470

East Asian (EAS) AF: 0.974 AC: 5045 AN: 5182

South Asian (SAS) AF: 0.956 AC: 4608 AN: 4822

European-Finnish (FIN) AF: 0.919 AC: 9746 AN: 10604

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.845 AC: 57505 AN: 68018

Other (OTH) AF: 0.869 AC: 1836 AN: 2112

Alfa AF: 0.879 Hom.: 10237

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
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12052316; hg19: chr2-98846093;