10-14899234-C-T

Position:

chr10-14899234-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000378289.8(DCLRE1C):c.1235G>A(p.Arg412Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0946 in 701,600 control chromosomes in the GnomAD database, including 4,107 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.088 ( 677 hom., cov: 32)

Exomes 𝑓: 0.096 ( 3430 hom. )

Consequence

DCLRE1C
ENST00000378289.8 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.621

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0060653985).

BP6

Variant 10-14899234-C-T is Benign according to our data. Variant chr10-14899234-C-T is described in ClinVar as [Benign]. Clinvar id is 1255460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUV39H2	NM_001193424.2 link	c.850-305C>T		intron_variant		ENST00000354919.11	NP_001180353.1	Q9H5I1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUV39H2	ENST00000354919.11 link	c.850-305C>T		intron_variant		5	NM_001193424.2	ENSP00000346997.6		Q9H5I1-1

Frequencies

GnomAD3 genomes

AF:

0.0880

AC:

13360

AN:

151864

Hom.:

677

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.0691

Gnomad AMR

AF:

0.0968

Gnomad ASJ

AF:

0.175

Gnomad EAS

AF:

0.0509

Gnomad SAS

AF:

0.208

Gnomad FIN

AF:

0.0324

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.0734

Gnomad OTH

AF:

0.0950

GnomAD3 exomes

AF:

0.111

AC:

14192

AN:

128002

Hom.:

1073

AF XY:

0.119

AC XY:

8347

AN XY:

70094

show subpopulations

Gnomad AFR exome

AF:

0.105

Gnomad AMR exome

AF:

0.112

Gnomad ASJ exome

AF:

0.167

Gnomad EAS exome

AF:

0.0388

Gnomad SAS exome

AF:

0.212

Gnomad FIN exome

AF:

0.0418

Gnomad NFE exome

AF:

0.0771

Gnomad OTH exome

AF:

0.118

GnomAD4 exome

AF:

0.0964

AC:

52998

AN:

549618

Hom.:

3430

Cov.:

AF XY:

0.104

AC XY:

30814

AN XY:

297546

show subpopulations

Gnomad4 AFR exome

AF:

0.108

Gnomad4 AMR exome

AF:

0.109

Gnomad4 ASJ exome

AF:

0.169

Gnomad4 EAS exome

AF:

0.0703

Gnomad4 SAS exome

AF:

0.211

Gnomad4 FIN exome

AF:

0.0400

Gnomad4 NFE exome

AF:

0.0752

Gnomad4 OTH exome

AF:

0.0973

GnomAD4 genome

AF:

0.0881

AC:

13385

AN:

151982

Hom.:

677

Cov.:

AF XY:

0.0892

AC XY:

6630

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.106

Gnomad4 AMR

AF:

0.0974

Gnomad4 ASJ

AF:

0.175

Gnomad4 EAS

AF:

0.0511

Gnomad4 SAS

AF:

0.208

Gnomad4 FIN

AF:

0.0324

Gnomad4 NFE

AF:

0.0734

Gnomad4 OTH

AF:

0.0940

Alfa

AF:

0.0685

Hom.:

116

Bravo

AF:

0.0916

TwinsUK

AF:

0.0720

AC:

267

ALSPAC

AF:

0.0724

AC:

279

ExAC

AF:

0.114

AC:

2236

Asia WGS

AF:

0.113

AC:

391

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 23% of patients studied by a panel of primary immunodeficiencies. Number of patients: 22. Only high quality variants are reported. -

Histiocytic medullary reticulosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Severe combined immunodeficiency due to DCLRE1C deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

8.9

DANN

Benign

0.84

Eigen

Benign

-0.82

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0062

LIST_S2

Benign

0.71

MetaRNN

Benign

0.0061

MetaSVM

Benign

-1.1

PROVEAN

Benign

-0.12

REVEL

Benign

0.078

Sift

Pathogenic

0.0

Sift4G

Benign

0.45

Polyphen

0.67

Vest4

0.036

ClinPred

0.015

GERP RS

0.82

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