chr10-14899187-G-A

Variant names:

• chr10-14899187-G-A
• rs148343292
• ENST00000378289.8:c.1282C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001193424.2(SUV39H2):​c.850-352G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00332 in 701,848 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0029 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (9 hom.)
• Consequence: SUV39H2 NM_001193424.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0110
• Publications: 1 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0052094758).
• BP6: Variant 10-14899187-G-A is Benign according to our data. Variant chr10-14899187-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1694558.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 440 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUV39H2	NM_001193424.2	c.850-352G>A		intron_variant	Intron 3 of 5	ENST00000354919.11	NP_001180353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUV39H2	ENST00000354919.11	c.850-352G>A		intron_variant	Intron 3 of 5	5	NM_001193424.2	ENSP00000346997.6

Frequencies

GnomAD3 genomes AF: 0.00289 AC: 440 AN: 152100 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000661

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00406

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00343 AC: 438 AN: 127866 AF XY: 0.00356

Gnomad AFR exome AF: 0.000986

Gnomad AMR exome AF: 0.00292

Gnomad ASJ exome AF: 0.0137

Gnomad EAS exome AF: 0.000287

Gnomad FIN exome AF: 0.000559

Gnomad NFE exome AF: 0.00404

Gnomad OTH exome AF: 0.00628

GnomAD4 exome AF: 0.00344 AC: 1888 AN: 549630 Hom.: 9 Cov.: 0 AF XY: 0.00349 AC XY: 1039 AN XY: 297552

African (AFR) AF: 0.000570 AC: 9 AN: 15786

American (AMR) AF: 0.00294 AC: 102 AN: 34664

Ashkenazi Jewish (ASJ) AF: 0.0157 AC: 314 AN: 20014

East Asian (EAS) AF: 0.000156 AC: 5 AN: 32096

South Asian (SAS) AF: 0.00108 AC: 68 AN: 62692

European-Finnish (FIN) AF: 0.000512 AC: 17 AN: 33182

Middle Eastern (MID) AF: 0.0104 AC: 41 AN: 3924

European-Non Finnish (NFE) AF: 0.00383 AC: 1212 AN: 316726

Other (OTH) AF: 0.00393 AC: 120 AN: 30546

GnomAD4 genome AF: 0.00289 AC: 440 AN: 152218 Hom.: 3 Cov.: 32 AF XY: 0.00259 AC XY: 193 AN XY: 74416

African (AFR) AF: 0.000650 AC: 27 AN: 41544

American (AMR) AF: 0.00373 AC: 57 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 53 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5172

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4824

European-Finnish (FIN) AF: 0.000661 AC: 7 AN: 10594

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00406 AC: 276 AN: 68008

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00360 Hom.: 0

Bravo AF: 0.00308

TwinsUK AF: 0.00270 AC: 10

ALSPAC AF: 0.00441 AC: 17

ExAC AF: 0.00304 AC: 54

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DCLRE1C: BP4, BS2; SUV39H2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.7
DANN	Benign	0.41
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0057	N
LIST_S2	Benign	0.37	T
MetaRNN	Benign	0.0052	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.011
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.088
MVP		0.061
ClinPred		0.0026	T
GERP RS		-1.5
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs148343292; hg19: chr10-14941186;