rs6715989

Variant names:

• chr2-98295808-G-A
• rs6715989
• NM_144992.5:c.3158-2099G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000477737.6(VWA3B):​c.3158-2099G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,134 control chromosomes in the GnomAD database, including 6,392 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 0.28 (6392 hom., cov: 33)
• Consequence: VWA3B ENST00000477737.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.692
• Publications: 3 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

ENSG00000222000 (HGNC:):

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 (AMR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000477737.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWA3B	NM_144992.5	MANE Select	c.3158-2099G>A		intron	N/A	NP_659429.4
	VWA3B	NM_001345864.2		c.2129-2099G>A		intron	N/A	NP_001332793.1
	VWA3B	NR_144296.2		n.3596-2099G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWA3B	ENST00000477737.6	TSL:1 MANE Select	c.3158-2099G>A		intron	N/A	ENSP00000417955.1
	VWA3B	ENST00000432242.5	TSL:1	n.*3061-2099G>A		intron	N/A	ENSP00000396734.1
	VWA3B	ENST00000495571.5	TSL:1	n.*1504-2099G>A		intron	N/A	ENSP00000437247.1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43028 AN: 152016 Hom.: 6374 Cov.: 33

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.283 AC: 43093 AN: 152134 Hom.: 6392 Cov.: 33 AF XY: 0.276 AC XY: 20566 AN XY: 74384

African (AFR) AF: 0.265 AC: 10975 AN: 41490

American (AMR) AF: 0.362 AC: 5540 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 958 AN: 3470

East Asian (EAS) AF: 0.217 AC: 1121 AN: 5168

South Asian (SAS) AF: 0.189 AC: 912 AN: 4820

European-Finnish (FIN) AF: 0.164 AC: 1734 AN: 10604

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.308 AC: 20931 AN: 67976

Other (OTH) AF: 0.302 AC: 639 AN: 2114

Alfa AF: 0.310 Hom.: 12465

Bravo AF: 0.301

Asia WGS AF: 0.197 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.23
DANN	Benign	0.30
PhyloP100		-0.69
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: rs6715989; hg19: chr2-98912271;