10-14899206-G-C

Variant names:

• chr10-14899206-G-C
• rs76797003
• ENST00000378289.8:c.1263C>G

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.850-333G>C variant causes a intron 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. 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: SUV39H2 NM_001193424.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.885
• 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=0.0077061355).
• 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.
• BS2: High AC in GnomAd4 at 451 AD gene.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00297 AC: 452 AN: 152088 Hom.: 2 Cov.: 32

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

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.: 8 Cov.: 0 AF XY: 0.00317 AC XY: 944 AN XY: 297694

African (AFR) AF: 0.00101 AC: 16 AN: 15798

American (AMR) AF: 0.00245 AC: 85 AN: 34700

Ashkenazi Jewish (ASJ) AF: 0.000150 AC: 3 AN: 20020

East Asian (EAS) AF: 0.0000312 AC: 1 AN: 32100

South Asian (SAS) AF: 0.000478 AC: 30 AN: 62758

European-Finnish (FIN) AF: 0.00238 AC: 79 AN: 33186

Middle Eastern (MID) AF: 0.000251 AC: 1 AN: 3978

European-Non Finnish (NFE) AF: 0.00478 AC: 1513 AN: 316782

Other (OTH) AF: 0.00344 AC: 105 AN: 30558

GnomAD4 genome AF: 0.00296 AC: 451 AN: 152206 Hom.: 2 Cov.: 32 AF XY: 0.00251 AC XY: 187 AN XY: 74422

African (AFR) AF: 0.000843 AC: 35 AN: 41514

American (AMR) AF: 0.00222 AC: 34 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00537 AC: 365 AN: 68000

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

Alfa AF: 0.00373 Hom.: 1

Bravo AF: 0.00292

TwinsUK AF: 0.00593 AC: 22

ALSPAC AF: 0.00415 AC: 16

ExAC AF: 0.000634 AC: 12

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	6.0
DANN	Benign	0.58
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.0077	T
MetaSVM	Benign	-0.95	T
PhyloP100		0.89
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.086
Sift	Pathogenic	0.0	D
Polyphen		0.0010	B
Vest4		0.10
MutPred		0.66		Gain of MoRF binding (P = 0.0054);
MVP		0.12
ClinPred		0.025	T
GERP RS		-0.59
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: rs76797003; hg19: chr10-14941205;