Variant chr19-45361959-T-C 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.1119-317A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 350,540 control chromosomes in the GnomAD database, including 64,626 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 32989 hom., cov: 30)

Exomes 𝑓: 0.56 ( 31637 hom. )

Consequence

ERCC2
NM_000400.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.47

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.03).

BP6

Variant 19-45361959-T-C is Benign according to our data. Variant chr19-45361959-T-C is described in ClinVar as [Benign]. Clinvar id is 1267350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.879 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.1119-317A>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.1119-317A>G		intron_variant		1	NM_000400.4	ENSP00000375809	P1	P18074-1

Frequencies

GnomAD3 genomes

AF:

0.640

AC:

97092

AN:

151754

Hom.:

32934

Cov.:

show subpopulations

Gnomad AFR

AF:

0.886

Gnomad AMI

AF:

0.569

Gnomad AMR

AF:

0.530

Gnomad ASJ

AF:

0.588

Gnomad EAS

AF:

0.497

Gnomad SAS

AF:

0.587

Gnomad FIN

AF:

0.568

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.546

Gnomad OTH

AF:

0.598

GnomAD4 exome

AF:

0.559

AC:

111104

AN:

198670

Hom.:

31637

Cov.:

AF XY:

0.563

AC XY:

60541

AN XY:

107518

show subpopulations

Gnomad4 AFR exome

AF:

0.887

Gnomad4 AMR exome

AF:

0.505

Gnomad4 ASJ exome

AF:

0.594

Gnomad4 EAS exome

AF:

0.495

Gnomad4 SAS exome

AF:

0.594

Gnomad4 FIN exome

AF:

0.558

Gnomad4 NFE exome

AF:

0.540

Gnomad4 OTH exome

AF:

0.554

GnomAD4 genome

AF:

0.640

AC:

97198

AN:

151870

Hom.:

32989

Cov.:

AF XY:

0.636

AC XY:

47174

AN XY:

74206

show subpopulations

Gnomad4 AFR

AF:

0.886

Gnomad4 AMR

AF:

0.529

Gnomad4 ASJ

AF:

0.588

Gnomad4 EAS

AF:

0.498

Gnomad4 SAS

AF:

0.587

Gnomad4 FIN

AF:

0.568

Gnomad4 NFE

AF:

0.545

Gnomad4 OTH

AF:

0.597

Alfa

AF:

0.606

Hom.:

3611

Bravo

AF:

0.649

Asia WGS

AF:

0.564

AC:

1963

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.12

DANN

Benign

0.30

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