1-1437035-TGGCTCCACTGCCCCTGGGCACCGG-T

Position:

• chr1-1437035-TGGCTCCACTGCCCCTGGGCACCGG-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP5

The NM_022834.5(VWA1):​c.186_209del​(p.Pro63_Ala70del) variant causes a inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: VWA1 NM_022834.5 inframe_deletion
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.00

Genes affected

VWA1 (HGNC:30910): (von Willebrand factor A domain containing 1) VWA1 belongs to the von Willebrand factor (VWF; MIM 613160) A (VWFA) domain superfamily of extracellular matrix proteins and appears to play a role in cartilage structure and function (Fitzgerald et al., 2002 [PubMed 12062410]).[supplied by OMIM, Nov 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_022834.5.
• PP5: Variant 1-1437035-TGGCTCCACTGCCCCTGGGCACCGG-T is Pathogenic according to our data. Variant chr1-1437035-TGGCTCCACTGCCCCTGGGCACCGG-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 830329.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWA1	NM_022834.5	c.186_209del	p.Pro63_Ala70del	inframe_deletion	2/3	ENST00000476993.2	NP_073745.2
VWA1	NM_199121.3	c.74-283_74-260del		intron_variant			NP_954572.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWA1	ENST00000476993.2	c.186_209del	p.Pro63_Ala70del	inframe_deletion	2/3	1	NM_022834.5	ENSP00000417185	P1
VWA1	ENST00000471398.1	c.306_329del	p.Pro103_Ala110del	inframe_deletion	2/2	3		ENSP00000464343
VWA1	ENST00000495558.1	c.81_104del	p.Pro28_Ala35del	inframe_deletion	2/2	2		ENSP00000463643
VWA1	ENST00000338660.5	c.74-283_74-260del		intron_variant		2		ENSP00000423404

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Neuromuscular disease Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

Section for Clinical Neurogenetics, University of Tübingen

Jan 01, 2020

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1638559065; hg19: chr1-1372415;