chr15-28114740-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_004667.6(HERC2):c.13785G>T(p.Glu4595Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,614,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_004667.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HERC2 | NM_004667.6 | c.13785G>T | p.Glu4595Asp | missense_variant | 90/93 | ENST00000261609.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HERC2 | ENST00000261609.13 | c.13785G>T | p.Glu4595Asp | missense_variant | 90/93 | 1 | NM_004667.6 | P1 | |
HERC2 | ENST00000566635.5 | n.910G>T | non_coding_transcript_exon_variant | 4/7 | 1 | ||||
HERC2 | ENST00000650509.1 | c.*899G>T | 3_prime_UTR_variant, NMD_transcript_variant | 36/39 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152120Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251494Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135922
GnomAD4 exome AF: 0.0000308 AC: 45AN: 1461890Hom.: 0 Cov.: 34 AF XY: 0.0000330 AC XY: 24AN XY: 727246
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152120Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74288
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 14, 2023 | The c.13785G>T (p.E4595D) alteration is located in exon 90 (coding exon 89) of the HERC2 gene. This alteration results from a G to T substitution at nucleotide position 13785, causing the glutamic acid (E) at amino acid position 4595 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at