2-98244594-C-T

Variant names:

• chr2-98244594-C-T
• rs4608580
• NM_144992.5:c.2674-5724C>T

Variant summary

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

The NM_144992.5(VWA3B):​c.2674-5724C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 151,930 control chromosomes in the GnomAD database, including 26,066 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 0.58 (26066 hom., cov: 32)
• Consequence: VWA3B NM_144992.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.519
• Publications: 1 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144992.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWA3B	NM_144992.5	MANE Select	c.2674-5724C>T		intron	N/A	NP_659429.4
	VWA3B	NM_001345864.2		c.1645-5724C>T		intron	N/A	NP_001332793.1
	VWA3B	NR_144296.2		n.2962-5724C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWA3B	ENST00000477737.6	TSL:1 MANE Select	c.2674-5724C>T		intron	N/A	ENSP00000417955.1	Q502W6-1
	VWA3B	ENST00000409460.5	TSL:1	n.2880-5724C>T		intron	N/A
	VWA3B	ENST00000432242.5	TSL:1	n.*2427-5724C>T		intron	N/A	ENSP00000396734.1	F8WD56

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88199 AN: 151812 Hom.: 26063 Cov.: 32

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.786

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.581 AC: 88235 AN: 151930 Hom.: 26066 Cov.: 32 AF XY: 0.584 AC XY: 43365 AN XY: 74272

African (AFR) AF: 0.625 AC: 25842 AN: 41358

American (AMR) AF: 0.528 AC: 8069 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 2141 AN: 3472

East Asian (EAS) AF: 0.785 AC: 4069 AN: 5182

South Asian (SAS) AF: 0.816 AC: 3934 AN: 4822

European-Finnish (FIN) AF: 0.525 AC: 5538 AN: 10542

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.538 AC: 36574 AN: 67960

Other (OTH) AF: 0.596 AC: 1259 AN: 2114

Alfa AF: 0.553 Hom.: 3052

Bravo AF: 0.578

Asia WGS AF: 0.786 AC: 2697 AN: 3436

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.5
DANN	Benign	0.81
PhyloP100		-0.52
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: rs4608580; hg19: chr2-98861057;