Variant chr19-45361758-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000400.4(ERCC2):c.1119-116C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0057 in 795,316 control chromosomes in the GnomAD database, including 140 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.019 ( 93 hom., cov: 33)

Exomes 𝑓: 0.0026 ( 47 hom. )

Consequence

ERCC2
NM_000400.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.53

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 19-45361758-G-C is Benign according to our data. Variant chr19-45361758-G-C is described in ClinVar as [Benign]. Clinvar id is 135530.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0635 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.1119-116C>G		intron_variant		ENST00000391945.10	NP_000391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC2	ENST00000391945.10 linkuse as main transcript	c.1119-116C>G		intron_variant		1	NM_000400.4	ENSP00000375809	P1	P18074-1

Frequencies

GnomAD3 genomes

AF:

0.0189

AC:

2875

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0655

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00707

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0163

GnomAD3 exomes

AF:

0.00512

AC:

934

AN:

182260

Hom.:

AF XY:

0.00373

AC XY:

366

AN XY:

98054

show subpopulations

Gnomad AFR exome

AF:

0.0723

Gnomad AMR exome

AF:

0.00379

Gnomad ASJ exome

AF:

0.000225

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000390

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000219

Gnomad OTH exome

AF:

0.00303

GnomAD4 exome

AF:

0.00257

AC:

1652

AN:

643058

Hom.:

Cov.:

AF XY:

0.00210

AC XY:

724

AN XY:

344654

show subpopulations

Gnomad4 AFR exome

AF:

0.0673

Gnomad4 AMR exome

AF:

0.00422

Gnomad4 ASJ exome

AF:

0.000198

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000121

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000184

Gnomad4 OTH exome

AF:

0.00645

GnomAD4 genome

AF:

0.0189

AC:

2885

AN:

152258

Hom.:

Cov.:

AF XY:

0.0178

AC XY:

1328

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0656

Gnomad4 AMR

AF:

0.00706

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.0114

Hom.:

Bravo

AF:

0.0226

Asia WGS

AF:

0.00751

AC:

AN:

3478

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

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.0060

DANN

Benign

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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