ENST00000378289.8:c.1263C>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000378289.8(DCLRE1C):c.1263C>G(p.Ser421Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00325 in 702,086 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0030 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 8 hom. )

Consequence

DCLRE1C
ENST00000378289.8 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.885

Publications

1 publications found

Variant links:

Genes affected

DCLRE1C (HGNC:17642): (DNA cross-link repair 1C) This gene encodes a nuclear protein that is involved in V(D)J recombination and DNA repair. The encoded protein has single-strand-specific 5'-3' exonuclease activity; it also exhibits endonuclease activity on 5' and 3' overhangs and hairpins. The protein also functions in the regulation of the cell cycle in response to DNA damage. Mutations in this gene can cause Athabascan-type severe combined immunodeficiency (SCIDA) and Omenn syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

DCLRE1C links:

SUV39H2 (HGNC:17287): (SUV39H2 histone lysine methyltransferase) Enables S-adenosyl-L-methionine binding activity; histone methyltransferase activity (H3-K9 specific); and zinc ion binding activity. Involved in chromatin assembly or disassembly and chromatin remodeling. Acts upstream of or within cellular response to hypoxia and negative regulation of transcription by RNA polymerase II. Located in chromatin. [provided by Alliance of Genome Resources, Apr 2022]

SUV39H2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0077061355).

BP6

Variant 10-14899206-G-C is Benign according to our data. Variant chr10-14899206-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2570766.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00296 (451/152206) while in subpopulation NFE AF = 0.00537 (365/68000). AF 95% confidence interval is 0.00491. There are 2 homozygotes in GnomAd4. There are 187 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUV39H2	NM_001193424.2 link	c.850-333G>C		intron_variant	Intron 3 of 5	ENST00000354919.11	NP_001180353.1	Q9H5I1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUV39H2	ENST00000354919.11 link	c.850-333G>C		intron_variant	Intron 3 of 5	5	NM_001193424.2	ENSP00000346997.6		Q9H5I1-1

Frequencies

GnomAD3 genomes

AF:

0.00297

AC:

452

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000846

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00537

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00254

AC:

325

AN:

128082

AF XY:

0.00254

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00214

Gnomad ASJ exome

AF:

0.000247

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00316

Gnomad NFE exome

AF:

0.00479

Gnomad OTH exome

AF:

0.00351

GnomAD4 exome

AF:

0.00333

AC:

1833

AN:

549880

Hom.:

Cov.:

AF XY:

0.00317

AC XY:

944

AN XY:

297694

show subpopulations

African (AFR)

AF:

0.00101

AC:

AN:

15798

American (AMR)

AF:

0.00245

AC:

AN:

34700

Ashkenazi Jewish (ASJ)

AF:

0.000150

AC:

AN:

20020

East Asian (EAS)

AF:

0.0000312

AC:

AN:

32100

South Asian (SAS)

AF:

0.000478

AC:

AN:

62758

European-Finnish (FIN)

AF:

0.00238

AC:

AN:

33186

Middle Eastern (MID)

AF:

0.000251

AC:

AN:

3978

European-Non Finnish (NFE)

AF:

0.00478

AC:

1513

AN:

316782

Other (OTH)

AF:

0.00344

AC:

105

AN:

30558

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

Heterozygous variant carriers

173

260

346

433

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00296

AC:

451

AN:

152206

Hom.:

Cov.:

AF XY:

0.00251

AC XY:

187

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.000843

AC:

AN:

41514

American (AMR)

AF:

0.00222

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00104

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00537

AC:

365

AN:

68000

Other (OTH)

AF:

0.00284

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

104

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00373

Hom.:

Bravo

AF:

0.00292

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00415

AC:

ExAC

AF:

0.000634

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

DCLRE1C: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.54

CADD

Benign

6.0

(source)

DANN

Benign

0.58

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.27

M_CAP

Benign

0.0074

MetaRNN

Benign

0.0077

MetaSVM

Benign

-0.95

PhyloP100

0.89

PROVEAN

Benign

-0.38

REVEL

Benign

0.086

Sift

Pathogenic

0.0

Polyphen

0.0010

Vest4

0.10

MutPred

0.66

Gain of MoRF binding (P = 0.0054);

MVP

0.12

ClinPred

0.025

GERP RS

-0.59

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

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ENST00000378289.8:c.1263C>G

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