rs8041209
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_004667.6(HERC2):c.7886-9C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,612,550 control chromosomes in the GnomAD database, including 21,469 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.22 ( 6879 hom., cov: 32)
Exomes 𝑓: 0.089 ( 14590 hom. )
Consequence
HERC2
NM_004667.6 splice_polypyrimidine_tract, intron
NM_004667.6 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.0002338
2
Clinical Significance
Conservation
PhyloP100: 0.0490
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 15-28198512-G-T is Benign according to our data. Variant chr15-28198512-G-T is described in ClinVar as [Benign]. Clinvar id is 1182699.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HERC2 | NM_004667.6 | c.7886-9C>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000261609.13 | NP_004658.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HERC2 | ENST00000261609.13 | c.7886-9C>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_004667.6 | ENSP00000261609 | P1 | |||
HERC2 | ENST00000567869.1 | n.1996-9C>A | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.215 AC: 32627AN: 151964Hom.: 6851 Cov.: 32
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GnomAD3 exomes AF: 0.143 AC: 35579AN: 249462Hom.: 5579 AF XY: 0.141 AC XY: 19041AN XY: 134848
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GnomAD4 exome AF: 0.0891 AC: 130115AN: 1460466Hom.: 14590 Cov.: 32 AF XY: 0.0930 AC XY: 67571AN XY: 726482
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GnomAD4 genome AF: 0.215 AC: 32705AN: 152084Hom.: 6879 Cov.: 32 AF XY: 0.216 AC XY: 16037AN XY: 74360
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 10, 2020 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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Name
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at