rs200823016
Positions:
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP2BP4_StrongBP6_Very_Strong
The NM_004667.6(HERC2):c.7316C>A(p.Ala2439Asp) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0024 ( 0 hom., cov: 16)
Exomes 𝑓: 0.0021 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
HERC2
NM_004667.6 missense
NM_004667.6 missense
Scores
1
2
14
Clinical Significance
Conservation
PhyloP100: 9.77
Genes affected
HERC2 (HGNC:4868): (HECT and RLD domain containing E3 ubiquitin protein ligase 2) This gene belongs to the HERC gene family that encodes a group of unusually large proteins, which contain multiple structural domains. All members have at least 1 copy of an N-terminal region showing homology to the cell cycle regulator RCC1 and a C-terminal HECT (homologous to E6-AP C terminus) domain found in a number of E3 ubiquitin protein ligases. Genetic variations in this gene are associated with skin/hair/eye pigmentation variability. Multiple pseudogenes of this gene are located on chromosomes 15 and 16. [provided by RefSeq, Mar 2012]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, HERC2
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0035172403).
BP6
?
Variant 15-28202511-G-T is Benign according to our data. Variant chr15-28202511-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 235233.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HERC2 | NM_004667.6 | c.7316C>A | p.Ala2439Asp | missense_variant | 46/93 | ENST00000261609.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HERC2 | ENST00000261609.13 | c.7316C>A | p.Ala2439Asp | missense_variant | 46/93 | 1 | NM_004667.6 | P1 | |
HERC2 | ENST00000567869.1 | n.1426C>A | non_coding_transcript_exon_variant | 1/10 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 252AN: 109510Hom.: 0 Cov.: 16 FAILED QC
GnomAD3 genomes
?
AF:
AC:
252
AN:
109510
Hom.:
Cov.:
16
FAILED QC
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00150 AC: 249AN: 166088Hom.: 0 AF XY: 0.00133 AC XY: 118AN XY: 88792
GnomAD3 exomes
AF:
AC:
249
AN:
166088
Hom.:
AF XY:
AC XY:
118
AN XY:
88792
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00207 AC: 2333AN: 1126826Hom.: 0 Cov.: 16 AF XY: 0.00178 AC XY: 1011AN XY: 567506
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
2333
AN:
1126826
Hom.:
Cov.:
16
AF XY:
AC XY:
1011
AN XY:
567506
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.00235 AC: 258AN: 109580Hom.: 0 Cov.: 16 AF XY: 0.00244 AC XY: 127AN XY: 52004
GnomAD4 genome
?
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
258
AN:
109580
Hom.:
Cov.:
16
AF XY:
AC XY:
127
AN XY:
52004
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
ExAC
?
AF:
AC:
324
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2023 | HERC2: PP2, BP4, BS1 - |
Benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Apr 25, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 06, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at