chr10-14899056-T-G

Variant names:

• chr10-14899056-T-G
• rs7896464
• ENST00000378289.8:c.*108A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001193424.2(SUV39H2):​c.850-483T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 587,386 control chromosomes in the GnomAD database, including 41,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (14805 hom., cov: 32)
  • Exomes 𝑓: 0.34 (26996 hom.)
• Consequence: SUV39H2 NM_001193424.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.13
• Publications: 4 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 10-14899056-T-G is Benign according to our data. Variant chr10-14899056-T-G is described in ClinVar as [Benign]. Clinvar id is 2688318.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUV39H2	NM_001193424.2	c.850-483T>G		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.850-483T>G		intron_variant	Intron 3 of 5	5	NM_001193424.2	ENSP00000346997.6

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62309 AN: 151940 Hom.: 14750 Cov.: 32

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.380

GnomAD4 exome AF: 0.336 AC: 146307 AN: 435328 Hom.: 26996 Cov.: 0 AF XY: 0.342 AC XY: 78240 AN XY: 228548

African (AFR) AF: 0.659 AC: 8161 AN: 12390

American (AMR) AF: 0.381 AC: 7303 AN: 19186

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 4771 AN: 13536

East Asian (EAS) AF: 0.469 AC: 14551 AN: 31008

South Asian (SAS) AF: 0.486 AC: 20298 AN: 41724

European-Finnish (FIN) AF: 0.222 AC: 6464 AN: 29124

Middle Eastern (MID) AF: 0.391 AC: 769 AN: 1968

European-Non Finnish (NFE) AF: 0.287 AC: 74973 AN: 260902

Other (OTH) AF: 0.354 AC: 9017 AN: 25490

GnomAD4 genome AF: 0.411 AC: 62426 AN: 152058 Hom.: 14805 Cov.: 32 AF XY: 0.412 AC XY: 30651 AN XY: 74334

African (AFR) AF: 0.658 AC: 27271 AN: 41432

American (AMR) AF: 0.384 AC: 5865 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1259 AN: 3470

East Asian (EAS) AF: 0.439 AC: 2275 AN: 5182

South Asian (SAS) AF: 0.495 AC: 2385 AN: 4814

European-Finnish (FIN) AF: 0.227 AC: 2403 AN: 10596

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.290 AC: 19686 AN: 67972

Other (OTH) AF: 0.378 AC: 800 AN: 2114

Alfa AF: 0.368 Hom.: 2042

Bravo AF: 0.430

Asia WGS AF: 0.448 AC: 1558 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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 22% of patients studied by a panel of primary immunodeficiencies. Number of patients: 21. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.43
DANN	Benign	0.26
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs7896464; hg19: chr10-14941055; COSMIC: COSV107374205; COSMIC: COSV107374205;