2-98244594-C-T

Position:

• chr2-98244594-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWA3B	NM_144992.5	c.2674-5724C>T		intron_variant		ENST00000477737.6	NP_659429.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWA3B	ENST00000477737.6	c.2674-5724C>T		intron_variant		1	NM_144992.5	ENSP00000417955.1

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

Gnomad4 AFR AF: 0.625

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.617

Gnomad4 EAS AF: 0.785

Gnomad4 SAS AF: 0.816

Gnomad4 FIN AF: 0.525

Gnomad4 NFE AF: 0.538

Gnomad4 OTH AF: 0.596

Alfa AF: 0.550 Hom.: 2907

Bravo AF: 0.578

Asia WGS AF: 0.786 AC: 2697 AN: 3436

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.5
DANN	Benign	0.81

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: rs4608580; hg19: chr2-98861057;