rs56170134

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000400.4(ERCC2):c.1119-25dupC 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
NM_000400.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: -0.478

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

cerebrooculofacioskeletal syndrome 2
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
trichothiodystrophy 1, photosensitive
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Illumina, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
xeroderma pigmentosum group D
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Laboratory for Molecular Medicine, ClinGen, Labcorp Genetics (formerly Invitae), G2P
sarcoma
Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
COFS syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
trichothiodystrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
xeroderma pigmentosum
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
xeroderma pigmentosum-Cockayne syndrome complex
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ERCC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
ERCC2	NM_000400.4 link	c.1119-25dupC		intron_variant	Intron 11 of 22	ENST00000391945.10	NP_000391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC2	ENST00000391945.10 link	c.1119-25dupC		intron_variant	Intron 11 of 22	1	NM_000400.4	ENSP00000375809.4

Frequencies

GnomAD3 genomes

AF:

0.0144

AC:

2191

AN:

152034

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00414

AC:

1034

AN:

249876

AF XY:

0.00310

show subpopulations

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 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.:

Cov.:

AF XY:

0.00148

AC XY:

1033

AN XY:

697814

show subpopulations

African (AFR)

AF:

0.0522

AC:

1671

AN:

32008

American (AMR)

AF:

0.00319

AC:

142

AN:

44578

Ashkenazi Jewish (ASJ)

AF:

0.000195

AC:

AN:

25692

East Asian (EAS)

AF:

0.000331

AC:

AN:

39320

South Asian (SAS)

AF:

0.0000943

AC:

AN:

84852

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53008

Middle Eastern (MID)

AF:

0.00124

AC:

AN:

5632

European-Non Finnish (NFE)

AF:

0.000278

AC:

293

AN:

1052578

Other (OTH)

AF:

0.00357

AC:

207

AN:

58016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

113

226

340

453

566

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0144

AC:

2192

AN:

152152

Hom.:

Cov.:

AF XY:

0.0138

AC XY:

1028

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0493

AC:

2047

AN:

41492

American (AMR)

AF:

0.00589

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00116

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000279

AC:

AN:

67982

Other (OTH)

AF:

0.0132

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

184

276

368

460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00232

Hom.:

Bravo

AF:

0.0175

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 24, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Other:1

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.48

BranchPoint Hunter

2.0

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over