6-31766314-G-T

Variant names:

• chr6-31766314-G-T
• rs1333760995
• NM_025258.3:c.2255C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_025258.3(VWA7):​c.2255C>A​(p.Ser752*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: VWA7 NM_025258.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890
• Publications: 0 publications found

Genes affected

VWA7 (HGNC:13939): (von Willebrand factor A domain containing 7) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWA7	NM_025258.3	c.2255C>A	p.Ser752*	stop_gained	Exon 15 of 17	ENST00000375688.5	NP_079534.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWA7	ENST00000375688.5	c.2255C>A	p.Ser752*	stop_gained	Exon 15 of 17	5	NM_025258.3	ENSP00000364840.4
VWA7	ENST00000467576.1	n.2118C>A		non_coding_transcript_exon_variant	Exon 15 of 15	2
VWA7	ENST00000486423.5	n.763C>A		non_coding_transcript_exon_variant	Exon 4 of 5	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00 AC: 0 AN: 242130 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	36
DANN	Benign	0.92
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.18	N
PhyloP100		0.089
Vest4		0.10
GERP RS		0.63
Mutation Taster		=76/124	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.24		Position offset: 5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1333760995; hg19: chr6-31734091;