Variant 19-45353210-G-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.1758+32C>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 1,610,776 control chromosomes in the GnomAD database, including 287,266 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33988 hom., cov: 30)

Exomes 𝑓: 0.59 ( 253278 hom. )

Consequence

ERCC2
NM_000400.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -4.93

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=-0.94).

BP6

Variant 19-45353210-G-C is Benign according to our data. Variant chr19-45353210-G-C is described in ClinVar as [Benign]. Clinvar id is 256016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
ERCC2	NM_000400.4 linkuse as main transcript	c.1758+32C>G	intron_variant	ENST00000391945.10
ERCC2	XM_011526611.3 linkuse as main transcript	c.1680+32C>G	intron_variant
ERCC2	XR_001753633.3 linkuse as main transcript	n.1791+32C>G	intron_variant, non_coding_transcript_variant
ERCC2	XR_007066680.1 linkuse as main transcript	n.1713+32C>G	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC2	ENST00000391945.10 linkuse as main transcript	c.1758+32C>G		intron_variant		1	NM_000400.4	P1	P18074-1

Frequencies

GnomAD3 genomes

AF:

0.656

AC:

99533

AN:

151742

Hom.:

33945

Cov.:

show subpopulations

Gnomad AFR

AF:

0.858

Gnomad AMI

AF:

0.764

Gnomad AMR

AF:

0.542

Gnomad ASJ

AF:

0.602

Gnomad EAS

AF:

0.510

Gnomad SAS

AF:

0.546

Gnomad FIN

AF:

0.646

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.583

Gnomad OTH

AF:

0.582

GnomAD3 exomes

AF:

0.589

AC:

147518

AN:

250360

Hom.:

44171

AF XY:

0.586

AC XY:

79370

AN XY:

135352

show subpopulations

Gnomad AFR exome

AF:

0.864

Gnomad AMR exome

AF:

0.523

Gnomad ASJ exome

AF:

0.612

Gnomad EAS exome

AF:

0.516

Gnomad SAS exome

AF:

0.556

Gnomad FIN exome

AF:

0.636

Gnomad NFE exome

AF:

0.582

Gnomad OTH exome

AF:

0.562

GnomAD4 exome

AF:

0.587

AC:

856584

AN:

1458916

Hom.:

253278

Cov.:

AF XY:

0.586

AC XY:

425137

AN XY:

725918

show subpopulations

Gnomad4 AFR exome

AF:

0.871

Gnomad4 AMR exome

AF:

0.522

Gnomad4 ASJ exome

AF:

0.602

Gnomad4 EAS exome

AF:

0.495

Gnomad4 SAS exome

AF:

0.560

Gnomad4 FIN exome

AF:

0.637

Gnomad4 NFE exome

AF:

0.584

Gnomad4 OTH exome

AF:

0.590

GnomAD4 genome

AF:

0.656

AC:

99632

AN:

151860

Hom.:

33988

Cov.:

AF XY:

0.652

AC XY:

48373

AN XY:

74232

show subpopulations

Gnomad4 AFR

AF:

0.858

Gnomad4 AMR

AF:

0.542

Gnomad4 ASJ

AF:

0.602

Gnomad4 EAS

AF:

0.510

Gnomad4 SAS

AF:

0.547

Gnomad4 FIN

AF:

0.646

Gnomad4 NFE

AF:

0.583

Gnomad4 OTH

AF:

0.582

Alfa

AF:

0.553

Hom.:

3166

Bravo

AF:

0.659

Asia WGS

AF:

0.544

AC:

1893

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Xeroderma pigmentosum, group D

Benign:2

Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Cerebrooculofacioskeletal syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Trichothiodystrophy 1, photosensitive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not provided

Benign:1

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

-0.94

CADD

Benign

0.033

DANN

Benign

0.46

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