rs3916823

Positions:

• chr19-45361933-CTTTT-C
• chr19-45361933-CTTTT-CTT
• chr19-45361933-CTTTT-CTTTTTTTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000400.4(ERCC2):​c.1119-295_1119-292del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 400,922 control chromosomes in the GnomAD database, including 3,405 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1109 hom., cov: 30)
  • Exomes 𝑓: 0.13 (2296 hom.)
• Consequence: ERCC2 NM_000400.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.818

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 -10 ACMG points.

• BP6: Variant 19-45361933-CTTTT-C is Benign according to our data. Variant chr19-45361933-CTTTT-C is described in ClinVar as [Benign]. Clinvar id is 1232033.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERCC2	NM_000400.4	c.1119-295_1119-292del		intron_variant		ENST00000391945.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC2	ENST00000391945.10	c.1119-295_1119-292del		intron_variant		1	NM_000400.4	P1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16116 AN: 151910 Hom.: 1105 Cov.: 30

Gnomad AFR AF: 0.0261

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.127 AC: 31617 AN: 248896 Hom.: 2296 AF XY: 0.128 AC XY: 16926 AN XY: 132534

Gnomad4 AFR exome AF: 0.0221

Gnomad4 AMR exome AF: 0.102

Gnomad4 ASJ exome AF: 0.148

Gnomad4 EAS exome AF: 0.0976

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.137

Gnomad4 OTH exome AF: 0.123

GnomAD4 genome AF: 0.106 AC: 16131 AN: 152026 Hom.: 1109 Cov.: 30 AF XY: 0.105 AC XY: 7824 AN XY: 74306

Gnomad4 AFR AF: 0.0260

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0493 Hom.: 41

Bravo AF: 0.104

Asia WGS AF: 0.127 AC: 439 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 07, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs3916823; hg19: chr19-45865191;