rs730880325
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_004963.4(GUCY2C):c.2270_2271insA(p.Asn757LysfsTer2) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,612,968 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
GUCY2C
NM_004963.4 frameshift
NM_004963.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.185
Genes affected
GUCY2C (HGNC:4688): (guanylate cyclase 2C) This gene encodes a transmembrane protein that functions as a receptor for endogenous peptides guanylin and uroguanylin, and the heat-stable E. coli enterotoxin. The encoded protein activates the cystic fibrosis transmembrane conductance regulator. Mutations in this gene are associated with familial diarrhea (autosomal dominant) and meconium ileus (autosomal recessive). [provided by RefSeq, Nov 2016]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 12-14625894-A-AT is Pathogenic according to our data. Variant chr12-14625894-A-AT is described in ClinVar as [Pathogenic]. Clinvar id is 31605.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GUCY2C | NM_004963.4 | c.2270_2271insA | p.Asn757LysfsTer2 | frameshift_variant | 21/27 | ENST00000261170.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GUCY2C | ENST00000261170.5 | c.2270_2271insA | p.Asn757LysfsTer2 | frameshift_variant | 21/27 | 1 | NM_004963.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152148Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460820Hom.: 0 Cov.: 29 AF XY: 0.00000275 AC XY: 2AN XY: 726760
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152148Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74330
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Meconium ileus Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 04, 2012 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at