Variant rs56170134 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000400.4(ERCC2):c.1119-25dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00293 in 1,547,836 control chromosomes in the GnomAD database, including 100 homozygotes. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.014 ( 52 hom., cov: 31)

Exomes 𝑓: 0.0017 ( 48 hom. )

Consequence

ERCC2
NM_000400.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: -0.478

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:

ERCC2 (HGNC:):

ERCC2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 19-45361666-C-CG is Benign according to our data. Variant chr19-45361666-C-CG is described in ClinVar as [Benign]. Clinvar id is 135525.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERCC2	NM_000400.4 linkuse as main transcript	c.1119-25dupC		intron_variant		ENST00000391945.10	NP_000391.1	P18074-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC2	ENST00000391945.10 linkuse as main transcript	c.1119-25dupC		intron_variant		1	NM_000400.4	ENSP00000375809.4		P18074-1

Frequencies

GnomAD3 genomes

AF:

0.0144

AC:

2191

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0495

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00590

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00414

AC:

1034

AN:

249876

Hom.:

AF XY:

0.00310

AC XY:

419

AN XY:

135216

show subpopulations

Gnomad AFR exome

AF:

0.0547

Gnomad AMR exome

AF:

0.00272

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.000762

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000257

Gnomad OTH exome

AF:

0.00213

GnomAD4 exome

AF:

0.00168

AC:

2346

AN:

1395684

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

1033

AN XY:

697814

show subpopulations

Gnomad4 AFR exome

AF:

0.0522

Gnomad4 AMR exome

AF:

0.00319

Gnomad4 ASJ exome

AF:

0.000195

Gnomad4 EAS exome

AF:

0.000331

Gnomad4 SAS exome

AF:

0.0000943

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000278

Gnomad4 OTH exome

AF:

0.00357

GnomAD4 genome

AF:

0.0144

AC:

2192

AN:

152152

Hom.:

Cov.:

AF XY:

0.0138

AC XY:

1028

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0493

Gnomad4 AMR

AF:

0.00589

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.00232

Hom.:

Bravo

AF:

0.0175

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 24, 2019

- -

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BranchPoint Hunter

2.0

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