Variant rs1799783 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_000400.4(ERCC2):c.247-35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 1,571,972 control chromosomes in the GnomAD database, including 253,709 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 32443 hom., cov: 32)

Exomes 𝑓: 0.56 ( 221266 hom. )

Consequence

ERCC2
NM_000400.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.77

Variant links:

Genes affected

ERCC2 (HGNC:3434): (ERCC excision repair 2, TFIIH core complex helicase subunit) The nucleotide excision repair pathway is a mechanism to repair damage to DNA. The protein encoded by this gene is involved in transcription-coupled nucleotide excision repair and is an integral member of the basal transcription factor BTF2/TFIIH complex. The gene product has ATP-dependent DNA helicase activity and belongs to the RAD3/XPD subfamily of helicases. Defects in this gene can result in three different disorders, the cancer-prone syndrome xeroderma pigmentosum complementation group D, trichothiodystrophy, and Cockayne syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

ERCC2 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 19-45368778-C-T is Benign according to our data. Variant chr19-45368778-C-T is described in ClinVar as [Benign]. Clinvar id is 256020.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERCC2	NM_000400.4 linkuse as main transcript	c.247-35G>A		intron_variant		ENST00000391945.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC2	ENST00000391945.10 linkuse as main transcript	c.247-35G>A		intron_variant		1	NM_000400.4	P1	P18074-1

Frequencies

GnomAD3 genomes

AF:

0.636

AC:

96627

AN:

151884

Hom.:

32391

Cov.:

show subpopulations

Gnomad AFR

AF:

0.869

Gnomad AMI

AF:

0.554

Gnomad AMR

AF:

0.525

Gnomad ASJ

AF:

0.584

Gnomad EAS

AF:

0.500

Gnomad SAS

AF:

0.586

Gnomad FIN

AF:

0.589

Gnomad MID

AF:

0.611

Gnomad NFE

AF:

0.546

Gnomad OTH

AF:

0.593

GnomAD3 exomes

AF:

0.575

AC:

129793

AN:

225820

Hom.:

37864

AF XY:

0.572

AC XY:

70054

AN XY:

122372

show subpopulations

Gnomad AFR exome

AF:

0.875

Gnomad AMR exome

AF:

0.516

Gnomad ASJ exome

AF:

0.602

Gnomad EAS exome

AF:

0.512

Gnomad SAS exome

AF:

0.597

Gnomad FIN exome

AF:

0.591

Gnomad NFE exome

AF:

0.550

Gnomad OTH exome

AF:

0.556

GnomAD4 exome

AF:

0.555

AC:

788211

AN:

1419970

Hom.:

221266

Cov.:

AF XY:

0.556

AC XY:

393502

AN XY:

707222

show subpopulations

Gnomad4 AFR exome

AF:

0.882

Gnomad4 AMR exome

AF:

0.512

Gnomad4 ASJ exome

AF:

0.592

Gnomad4 EAS exome

AF:

0.494

Gnomad4 SAS exome

AF:

0.600

Gnomad4 FIN exome

AF:

0.589

Gnomad4 NFE exome

AF:

0.542

Gnomad4 OTH exome

AF:

0.567

GnomAD4 genome

AF:

0.636

AC:

96731

AN:

152002

Hom.:

32443

Cov.:

AF XY:

0.633

AC XY:

47048

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.869

Gnomad4 AMR

AF:

0.525

Gnomad4 ASJ

AF:

0.584

Gnomad4 EAS

AF:

0.501

Gnomad4 SAS

AF:

0.586

Gnomad4 FIN

AF:

0.589

Gnomad4 NFE

AF:

0.546

Gnomad4 OTH

AF:

0.593

Alfa

AF:

0.597

Hom.:

5112

Bravo

AF:

0.643

Asia WGS

AF:

0.563

AC:

1961

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Xeroderma pigmentosum, group D

Benign:2

Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Cerebrooculofacioskeletal syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Trichothiodystrophy 1, photosensitive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.82

DANN

Benign

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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