Variant chr15-28114598-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004667.6(HERC2):c.13913+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.96 in 1,609,068 control chromosomes in the GnomAD database, including 751,615 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.85 ( 58175 hom., cov: 31)

Exomes 𝑓: 0.97 ( 693440 hom. )

Consequence

HERC2
NM_004667.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.539

Variant links:

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]

HERC2 links:

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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=-0.85).

BP6

Variant 15-28114598-G-A is Benign according to our data. Variant chr15-28114598-G-A is described in ClinVar as [Benign]. Clinvar id is 1285341.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HERC2	NM_004667.6 linkuse as main transcript	c.13913+14C>T		intron_variant		ENST00000261609.13

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
HERC2	ENST00000261609.13 linkuse as main transcript	c.13913+14C>T	intron_variant	1	NM_004667.6	P1
HERC2	ENST00000566635.5 linkuse as main transcript	n.1038+14C>T	intron_variant, non_coding_transcript_variant	1
HERC2	ENST00000650509.1 linkuse as main transcript	c.*1027+14C>T	intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.849

AC:

128910

AN:

151902

Hom.:

58175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.505

Gnomad AMI

AF:

0.980

Gnomad AMR

AF:

0.940

Gnomad ASJ

AF:

0.969

Gnomad EAS

AF:

0.978

Gnomad SAS

AF:

0.863

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.886

Gnomad NFE

AF:

0.993

Gnomad OTH

AF:

0.875

GnomAD3 exomes

AF:

0.938

AC:

233938

AN:

249496

Hom.:

111720

AF XY:

0.942

AC XY:

127075

AN XY:

134906

show subpopulations

Gnomad AFR exome

AF:

0.489

Gnomad AMR exome

AF:

0.970

Gnomad ASJ exome

AF:

0.968

Gnomad EAS exome

AF:

0.973

Gnomad SAS exome

AF:

0.861

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.992

Gnomad OTH exome

AF:

0.957

GnomAD4 exome

AF:

0.972

AC:

1416156

AN:

1457048

Hom.:

693440

Cov.:

AF XY:

0.970

AC XY:

702478

AN XY:

724050

show subpopulations

Gnomad4 AFR exome

AF:

0.484

Gnomad4 AMR exome

AF:

0.967

Gnomad4 ASJ exome

AF:

0.968

Gnomad4 EAS exome

AF:

0.979

Gnomad4 SAS exome

AF:

0.866

Gnomad4 FIN exome

AF:

0.999

Gnomad4 NFE exome

AF:

0.995

Gnomad4 OTH exome

AF:

0.946

GnomAD4 genome

AF:

0.848

AC:

128941

AN:

152020

Hom.:

58175

Cov.:

AF XY:

0.852

AC XY:

63279

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.505

Gnomad4 AMR

AF:

0.941

Gnomad4 ASJ

AF:

0.969

Gnomad4 EAS

AF:

0.978

Gnomad4 SAS

AF:

0.862

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.993

Gnomad4 OTH

AF:

0.869

Alfa

AF:

0.942

Hom.:

18158

Bravo

AF:

0.831

Asia WGS

AF:

0.876

AC:

3045

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Developmental delay with autism spectrum disorder and gait instability

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.1

DANN

Benign

0.42

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over