2-98210693-T-G

Variant names:

• chr2-98210693-T-G
• rs7603439
• NM_144992.5:c.1738-1237T>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.1738-1237T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.887 in 152,146 control chromosomes in the GnomAD database, including 60,101 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 0.89 (60101 hom., cov: 30)
• Consequence: VWA3B NM_144992.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.758
• Publications: 0 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWA3B	NM_144992.5	MANE Select	c.1738-1237T>G		intron	N/A	NP_659429.4
	VWA3B	NM_001345864.2		c.709-1237T>G		intron	N/A	NP_001332793.1
	VWA3B	NR_144296.2		n.1805-1237T>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWA3B	ENST00000477737.6	TSL:1 MANE Select	c.1738-1237T>G		intron	N/A	ENSP00000417955.1
	VWA3B	ENST00000409460.5	TSL:1	n.1944-1237T>G		intron	N/A
	VWA3B	ENST00000416277.5	TSL:1	n.*385-1237T>G		intron	N/A	ENSP00000411168.1

Frequencies

GnomAD3 genomes AF: 0.887 AC: 134860 AN: 152028 Hom.: 60046 Cov.: 30

Gnomad AFR AF: 0.944

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.852

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.956

Gnomad FIN AF: 0.918

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.858

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

GnomAD4 genome AF: 0.887 AC: 134974 AN: 152146 Hom.: 60101 Cov.: 30 AF XY: 0.891 AC XY: 66294 AN XY: 74376

African (AFR) AF: 0.944 AC: 39189 AN: 41498

American (AMR) AF: 0.884 AC: 13505 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.852 AC: 2959 AN: 3472

East Asian (EAS) AF: 0.973 AC: 5022 AN: 5160

South Asian (SAS) AF: 0.956 AC: 4606 AN: 4820

European-Finnish (FIN) AF: 0.918 AC: 9733 AN: 10608

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.840 AC: 57115 AN: 67984

Other (OTH) AF: 0.860 AC: 1817 AN: 2114

Alfa AF: 0.858 Hom.: 28937

Bravo AF: 0.885

Asia WGS AF: 0.953 AC: 3315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.73
PhyloP100		-0.76
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: rs7603439; hg19: chr2-98827156;