chr6-31767454-T-C

Position:

• chr6-31767454-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025258.3(VWA7):​c.1697A>G​(p.Gln566Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: VWA7 NM_025258.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.31

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11203405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VWA7	NM_025258.3	c.1697A>G	p.Gln566Arg	missense_variant	12/17	ENST00000375688.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VWA7	ENST00000375688.5	c.1697A>G	p.Gln566Arg	missense_variant	12/17	5	NM_025258.3	P1
VWA7	ENST00000467576.1	n.1560A>G		non_coding_transcript_exon_variant	12/15	2
VWA7	ENST00000486423.5	n.127A>G		non_coding_transcript_exon_variant	2/5	5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 10, 2024

The c.1697A>G (p.Q566R) alteration is located in exon 12 (coding exon 11) of the VWA7 gene. This alteration results from a A to G substitution at nucleotide position 1697, causing the glutamine (Q) at amino acid position 566 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.65	D
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.050
Sift	Benign	0.49	T
Sift4G	Benign	0.66	T
Polyphen		0.0010	B
Vest4		0.22
MutPred		0.44		Gain of MoRF binding (P = 0.0142);
MVP		0.12
MPC		0.31
ClinPred		0.10	T
GERP RS		2.5
Varity_R		0.075
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-31735231;