10-14899234-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001193424.2(SUV39H2):c.850-305C>T variant causes a intron 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. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.088 ( 677 hom., cov: 32)

Exomes 𝑓: 0.096 ( 3430 hom. )

Consequence

SUV39H2
NM_001193424.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.621

Publications

3 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 -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 rank	MANE	Protein	UniProt
SUV39H2	NM_001193424.2 link	c.850-305C>T		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.850-305C>T		intron_variant	Intron 3 of 5	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

GnomAD2 exomes

AF:

0.111

AC:

14192

AN:

128002

AF XY:

0.119

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 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

African (AFR)

AF:

0.108

AC:

1698

AN:

15788

American (AMR)

AF:

0.109

AC:

3775

AN:

34678

Ashkenazi Jewish (ASJ)

AF:

0.169

AC:

3372

AN:

19994

East Asian (EAS)

AF:

0.0703

AC:

2255

AN:

32098

South Asian (SAS)

AF:

0.211

AC:

13233

AN:

62628

European-Finnish (FIN)

AF:

0.0400

AC:

1329

AN:

33188

Middle Eastern (MID)

AF:

0.137

AC:

544

AN:

3978

European-Non Finnish (NFE)

AF:

0.0752

AC:

23819

AN:

316718

Other (OTH)

AF:

0.0973

AC:

2973

AN:

30548

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

2196

4393

6589

8786

10982

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0881

AC:

13385

AN:

151982

Hom.:

677

Cov.:

AF XY:

0.0892

AC XY:

6630

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.106

AC:

4391

AN:

41434

American (AMR)

AF:

0.0974

AC:

1487

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.175

AC:

607

AN:

3468

East Asian (EAS)

AF:

0.0511

AC:

264

AN:

5170

South Asian (SAS)

AF:

0.208

AC:

1000

AN:

4812

European-Finnish (FIN)

AF:

0.0324

AC:

341

AN:

10540

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0734

AC:

4987

AN:

67978

Other (OTH)

AF:

0.0940

AC:

198

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

606

1211

1817

2422

3028

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0739

Hom.:

157

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

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Severe combined immunodeficiency due to DCLRE1C deficiency

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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

PhyloP100

-0.62

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

Mutation Taster

=100/0

polymorphism (auto)

(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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10-14899234-C-T

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