Variant rs1799788 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 ENST00000391945.10(ERCC2):c.1832-26C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0566 in 1,609,886 control chromosomes in the GnomAD database, including 2,855 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.044 ( 159 hom., cov: 31)

Exomes 𝑓: 0.058 ( 2696 hom. )

Consequence

ERCC2
ENST00000391945.10 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.211

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=-0.87).

BP6

Variant 19-45352842-G-A is Benign according to our data. Variant chr19-45352842-G-A is described in ClinVar as [Benign]. Clinvar id is 1248418.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-45352842-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
ERCC2	NM_000400.4 linkuse as main transcript	c.1832-26C>T	intron_variant	ENST00000391945.10	NP_000391.1
ERCC2	XM_011526611.3 linkuse as main transcript	c.1754-26C>T	intron_variant		XP_011524913.1
ERCC2	XR_001753633.3 linkuse as main transcript	n.1865-26C>T	intron_variant, non_coding_transcript_variant
ERCC2	XR_007066680.1 linkuse as main transcript	n.1787-26C>T	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC2	ENST00000391945.10 linkuse as main transcript	c.1832-26C>T		intron_variant		1	NM_000400.4	ENSP00000375809	P1	P18074-1

Frequencies

GnomAD3 genomes

AF:

0.0443

AC:

6728

AN:

151894

Hom.:

157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0297

Gnomad AMI

AF:

0.0176

Gnomad AMR

AF:

0.0288

Gnomad ASJ

AF:

0.0427

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.0465

Gnomad FIN

AF:

0.0444

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0601

Gnomad OTH

AF:

0.0480

GnomAD3 exomes

AF:

0.0467

AC:

11616

AN:

248820

Hom.:

341

AF XY:

0.0481

AC XY:

6483

AN XY:

134700

show subpopulations

Gnomad AFR exome

AF:

0.0311

Gnomad AMR exome

AF:

0.0225

Gnomad ASJ exome

AF:

0.0488

Gnomad EAS exome

AF:

0.000327

Gnomad SAS exome

AF:

0.0491

Gnomad FIN exome

AF:

0.0499

Gnomad NFE exome

AF:

0.0620

Gnomad OTH exome

AF:

0.0548

GnomAD4 exome

AF:

0.0579

AC:

84444

AN:

1457874

Hom.:

2696

Cov.:

AF XY:

0.0578

AC XY:

41918

AN XY:

725458

show subpopulations

Gnomad4 AFR exome

AF:

0.0288

Gnomad4 AMR exome

AF:

0.0238

Gnomad4 ASJ exome

AF:

0.0509

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0498

Gnomad4 FIN exome

AF:

0.0501

Gnomad4 NFE exome

AF:

0.0636

Gnomad4 OTH exome

AF:

0.0560

GnomAD4 genome

AF:

0.0443

AC:

6738

AN:

152012

Hom.:

159

Cov.:

AF XY:

0.0431

AC XY:

3206

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.0299

Gnomad4 AMR

AF:

0.0288

Gnomad4 ASJ

AF:

0.0427

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.0465

Gnomad4 FIN

AF:

0.0444

Gnomad4 NFE

AF:

0.0601

Gnomad4 OTH

AF:

0.0475

Alfa

AF:

0.0521

Hom.:

Bravo

AF:

0.0430

Asia WGS

AF:

0.0200

AC:

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	Jan 10, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.64

DANN

Benign

0.76

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