16-68813484-A-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_004360.5(CDH1):c.1309A>T(p.Lys437*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000137 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_004360.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDH1 | NM_004360.5 | c.1309A>T | p.Lys437* | stop_gained | Exon 9 of 16 | ENST00000261769.10 | NP_004351.1 | |
CDH1 | NM_001317185.2 | c.-307A>T | 5_prime_UTR_variant | Exon 9 of 16 | NP_001304114.1 | |||
CDH1 | NM_001317186.2 | c.-511A>T | 5_prime_UTR_variant | Exon 9 of 15 | NP_001304115.1 | |||
CDH1 | NM_001317184.2 | c.1137+1221A>T | intron_variant | Intron 8 of 14 | NP_001304113.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461860Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727240
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Pathogenic:1
The p.K437* pathogenic mutation (also known as c.1309A>T), located in coding exon 9 of the CDH1 gene, results from an A to T substitution at nucleotide position 1309. This changes the amino acid from a lysine to a stop codon within coding exon 9. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.