Variant 19-45361744-C-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_000400.4(ERCC2):c.1119-102G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 868,646 control chromosomes in the GnomAD database, including 147,608 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 32321 hom., cov: 31)

Exomes 𝑓: 0.56 ( 115287 hom. )

Consequence

ERCC2
NM_000400.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.161

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 19-45361744-C-A is Benign according to our data. Variant chr19-45361744-C-A is described in ClinVar as [Benign]. Clinvar id is 135529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.853 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.1119-102G>T		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.1119-102G>T		intron_variant		1	NM_000400.4	ENSP00000375809.4		P18074-1

Frequencies

GnomAD3 genomes

AF:

0.636

AC:

96572

AN:

151800

Hom.:

32270

Cov.:

show subpopulations

Gnomad AFR

AF:

0.861

Gnomad AMI

AF:

0.571

Gnomad AMR

AF:

0.528

Gnomad ASJ

AF:

0.588

Gnomad EAS

AF:

0.498

Gnomad SAS

AF:

0.588

Gnomad FIN

AF:

0.593

Gnomad MID

AF:

0.615

Gnomad NFE

AF:

0.549

Gnomad OTH

AF:

0.595

GnomAD3 exomes

AF:

0.581

AC:

117148

AN:

201574

Hom.:

34430

AF XY:

0.579

AC XY:

62969

AN XY:

108770

show subpopulations

Gnomad AFR exome

AF:

0.870

Gnomad AMR exome

AF:

0.521

Gnomad ASJ exome

AF:

0.611

Gnomad EAS exome

AF:

0.511

Gnomad SAS exome

AF:

0.604

Gnomad FIN exome

AF:

0.601

Gnomad NFE exome

AF:

0.559

Gnomad OTH exome

AF:

0.566

GnomAD4 exome

AF:

0.564

AC:

404426

AN:

716726

Hom.:

115287

Cov.:

AF XY:

0.566

AC XY:

215607

AN XY:

380928

show subpopulations

Gnomad4 AFR exome

AF:

0.861

Gnomad4 AMR exome

AF:

0.516

Gnomad4 ASJ exome

AF:

0.599

Gnomad4 EAS exome

AF:

0.491

Gnomad4 SAS exome

AF:

0.603

Gnomad4 FIN exome

AF:

0.593

Gnomad4 NFE exome

AF:

0.550

Gnomad4 OTH exome

AF:

0.574

GnomAD4 genome

AF:

0.636

AC:

96676

AN:

151920

Hom.:

32321

Cov.:

AF XY:

0.634

AC XY:

47050

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.861

Gnomad4 AMR

AF:

0.528

Gnomad4 ASJ

AF:

0.588

Gnomad4 EAS

AF:

0.498

Gnomad4 SAS

AF:

0.588

Gnomad4 FIN

AF:

0.593

Gnomad4 NFE

AF:

0.549

Gnomad4 OTH

AF:

0.594

Alfa

AF:

0.564

Hom.:

41452

Bravo

AF:

0.643

Asia WGS

AF:

0.561

AC:

1956

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

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

-0.92

CADD

Benign

9.5

DANN

Benign

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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