chr15-28111760-ATCTTAGTGTCC-A
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1
The NM_004667.6(HERC2):c.14497_*2delGGACACTAAGA(p.Gly4833fs) variant causes a frameshift, stop lost change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,612,092 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_004667.6 frameshift, stop_lost
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HERC2 | NM_004667.6 | c.14497_*2delGGACACTAAGA | p.Gly4833fs | frameshift_variant, stop_lost | Exon 93 of 93 | ENST00000261609.13 | NP_004658.3 | |
HERC2 | NM_004667.6 | c.14499_*2delGGACACTAAGA | 3_prime_UTR_variant | Exon 93 of 93 | ENST00000261609.13 | NP_004658.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HERC2 | ENST00000261609.13 | c.14497_*2delGGACACTAAGA | p.Gly4833fs | frameshift_variant, stop_lost | Exon 93 of 93 | 1 | NM_004667.6 | ENSP00000261609.8 | ||
HERC2 | ENST00000261609 | c.14499_*2delGGACACTAAGA | 3_prime_UTR_variant | Exon 93 of 93 | 1 | NM_004667.6 | ENSP00000261609.8 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152164Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251362Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135848
GnomAD4 exome AF: 0.0000322 AC: 47AN: 1459928Hom.: 0 AF XY: 0.0000344 AC XY: 25AN XY: 725778
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152164Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74326
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant summary: HERC2 c.14497_*2del11 (p.Gly4833TrpfsX8) causes a frameshift which results in an extension of the protein. The variant allele was found at a frequency of 4e-05 in 251362 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in HERC2 causing Intellectual Developmental Disorder, Autosomal Recessive 38, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.14497_*2del11 in individuals affected with Intellectual Developmental Disorder, Autosomal Recessive 38 and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at