Variant 19-45361788-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000391945.10(ERCC2):c.1119-146T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0226 in 703,866 control chromosomes in the GnomAD database, including 251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 47 hom., cov: 33)

Exomes 𝑓: 0.023 ( 204 hom. )

Consequence

ERCC2
ENST00000391945.10 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: 0.0230

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=-0.9).

BP6

Variant 19-45361788-A-C is Benign according to our data. Variant chr19-45361788-A-C is described in ClinVar as [Benign]. Clinvar id is 135531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0195 (2964/152146) while in subpopulation NFE AF= 0.0261 (1777/67990). AF 95% confidence interval is 0.0251. There are 47 homozygotes in gnomad4. There are 1442 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERCC2	NM_000400.4 linkuse as main transcript	c.1119-146T>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.1119-146T>G		intron_variant		1	NM_000400.4	ENSP00000375809	P1	P18074-1

Frequencies

GnomAD3 genomes

AF:

0.0195

AC:

2963

AN:

152028

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00500

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0119

Gnomad ASJ

AF:

0.0541

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.0514

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0261

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.0211

AC:

3165

AN:

149676

Hom.:

AF XY:

0.0204

AC XY:

1627

AN XY:

79732

show subpopulations

Gnomad AFR exome

AF:

0.00349

Gnomad AMR exome

AF:

0.0116

Gnomad ASJ exome

AF:

0.0636

Gnomad EAS exome

AF:

0.0000863

Gnomad SAS exome

AF:

0.00479

Gnomad FIN exome

AF:

0.0530

Gnomad NFE exome

AF:

0.0268

Gnomad OTH exome

AF:

0.0282

GnomAD4 exome

AF:

0.0234

AC:

12914

AN:

551720

Hom.:

204

Cov.:

AF XY:

0.0223

AC XY:

6661

AN XY:

298342

show subpopulations

Gnomad4 AFR exome

AF:

0.00368

Gnomad4 AMR exome

AF:

0.0121

Gnomad4 ASJ exome

AF:

0.0597

Gnomad4 EAS exome

AF:

0.0000317

Gnomad4 SAS exome

AF:

0.00517

Gnomad4 FIN exome

AF:

0.0446

Gnomad4 NFE exome

AF:

0.0267

Gnomad4 OTH exome

AF:

0.0244

GnomAD4 genome

AF:

0.0195

AC:

2964

AN:

152146

Hom.:

Cov.:

AF XY:

0.0194

AC XY:

1442

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00499

Gnomad4 AMR

AF:

0.0119

Gnomad4 ASJ

AF:

0.0541

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.0514

Gnomad4 NFE

AF:

0.0261

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.0260

Hom.:

Bravo

AF:

0.0166

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 07, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.90

CADD

Benign

2.3

DANN

Benign

0.64

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