rs1799783

chr19-45368778-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000400.4(ERCC2):c.247-35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 1,571,972 control chromosomes in the GnomAD database, including 253,709 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (32443 hom., cov: 32)
  • Exomes 𝑓: 0.56 (221266 hom.)
• Consequence: ERCC2 NM_000400.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.77

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 19-45368778-C-T is Benign according to our data. Variant chr19-45368778-C-T is described in ClinVar as [Benign]. Clinvar id is 256020.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERCC2	NM_000400.4	c.247-35G>A		intron_variant		ENST00000391945.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC2	ENST00000391945.10	c.247-35G>A		intron_variant		1	NM_000400.4	P1

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96627 AN: 151884 Hom.: 32391 Cov.: 32

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.593

GnomAD3 exomes AF: 0.575 AC: 129793 AN: 225820 Hom.: 37864 AF XY: 0.572 AC XY: 70054 AN XY: 122372

Gnomad AFR exome AF: 0.875

Gnomad AMR exome AF: 0.516

Gnomad ASJ exome AF: 0.602

Gnomad EAS exome AF: 0.512

Gnomad SAS exome AF: 0.597

Gnomad FIN exome AF: 0.591

Gnomad NFE exome AF: 0.550

Gnomad OTH exome AF: 0.556

GnomAD4 exome AF: 0.555 AC: 788211 AN: 1419970 Hom.: 221266 Cov.: 25 AF XY: 0.556 AC XY: 393502 AN XY: 707222

Gnomad4 AFR exome AF: 0.882

Gnomad4 AMR exome AF: 0.512

Gnomad4 ASJ exome AF: 0.592

Gnomad4 EAS exome AF: 0.494

Gnomad4 SAS exome AF: 0.600

Gnomad4 FIN exome AF: 0.589

Gnomad4 NFE exome AF: 0.542

Gnomad4 OTH exome AF: 0.567

GnomAD4 genome AF: 0.636 AC: 96731 AN: 152002 Hom.: 32443 Cov.: 32 AF XY: 0.633 AC XY: 47048 AN XY: 74272

Gnomad4 AFR AF: 0.869

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.501

Gnomad4 SAS AF: 0.586

Gnomad4 FIN AF: 0.589

Gnomad4 NFE AF: 0.546

Gnomad4 OTH AF: 0.593

Alfa AF: 0.597 Hom.: 5112

Bravo AF: 0.643

Asia WGS AF: 0.563 AC: 1961 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Xeroderma pigmentosum, group D Benign:2

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

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	-0.85
Cadd	Benign	0.82
Dann	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs1799783; hg19: chr19-45872036;