rs587776510

Positions:

• chr17-78993846-G-GGCGGC

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The ENST00000392446.10(CANT1):​c.909_910insGCCGC​(p.Gln304AlafsTer20) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CANT1 ENST00000392446.10 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.57

Genes affected

CANT1 (HGNC:19721): (calcium activated nucleotidase 1) This protein encoded by this gene belongs to the apyrase family. It functions as a calcium-dependent nucleotidase with a preference for UDP. Mutations in this gene are associated with Desbuquois dysplasia with hand anomalies. Alternatively spliced transcript variants have been noted for this gene.[provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 6 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-78993846-G-GGCGGC is Pathogenic according to our data. Variant chr17-78993846-G-GGCGGC is described in ClinVar as [Pathogenic]. Clinvar id is 281.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CANT1	NM_001159773.2	c.909_910insGCCGC	p.Gln304AlafsTer20	frameshift_variant	5/5	ENST00000392446.10	NP_001153245.1
CANT1	NM_001159772.2	c.909_910insGCCGC	p.Gln304AlafsTer20	frameshift_variant	6/6		NP_001153244.1
CANT1	NM_138793.4	c.909_910insGCCGC	p.Gln304AlafsTer20	frameshift_variant	4/4		NP_620148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CANT1	ENST00000392446.10	c.909_910insGCCGC	p.Gln304AlafsTer20	frameshift_variant	5/5	1	NM_001159773.2	ENSP00000376241	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Desbuquois dysplasia 1 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 01, 2009

- -

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: rs587776510; hg19: chr17-76989928;