rs56170134

Positions:

• chr19-45361666-C-CG
• chr19-45361666-C-CGG

Variant summary

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

The ENST00000391945.10(ERCC2):​c.1119-25_1119-24insC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00293 in 1,547,836 control chromosomes in the GnomAD database, including 100 homozygotes. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.014 (52 hom., cov: 31)
  • Exomes 𝑓: 0.0017 (48 hom.)
• Consequence: ERCC2 ENST00000391945.10 intron
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: -0.478

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 19-45361666-C-CG is Benign according to our data. Variant chr19-45361666-C-CG is described in ClinVar as [Benign]. Clinvar id is 135525.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERCC2	NM_000400.4	c.1119-25_1119-24insC		intron_variant		ENST00000391945.10	NP_000391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC2	ENST00000391945.10	c.1119-25_1119-24insC		intron_variant		1	NM_000400.4	ENSP00000375809	P1

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2191 AN: 152034 Hom.: 52 Cov.: 31

Gnomad AFR AF: 0.0495

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00590

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.00414 AC: 1034 AN: 249876 Hom.: 22 AF XY: 0.00310 AC XY: 419 AN XY: 135216

Gnomad AFR exome AF: 0.0547

Gnomad AMR exome AF: 0.00272

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.000762

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000257

Gnomad OTH exome AF: 0.00213

GnomAD4 exome AF: 0.00168 AC: 2346 AN: 1395684 Hom.: 48 Cov.: 22 AF XY: 0.00148 AC XY: 1033 AN XY: 697814

Gnomad4 AFR exome AF: 0.0522

Gnomad4 AMR exome AF: 0.00319

Gnomad4 ASJ exome AF: 0.000195

Gnomad4 EAS exome AF: 0.000331

Gnomad4 SAS exome AF: 0.0000943

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000278

Gnomad4 OTH exome AF: 0.00357

GnomAD4 genome AF: 0.0144 AC: 2192 AN: 152152 Hom.: 52 Cov.: 31 AF XY: 0.0138 AC XY: 1028 AN XY: 74424

Gnomad4 AFR AF: 0.0493

Gnomad4 AMR AF: 0.00589

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.00232 Hom.: 2

Bravo AF: 0.0175

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 24, 2019

- -

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
BranchPoint Hunter		2.0

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: rs56170134; hg19: chr19-45864924;