10-14899056-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000378289.8(DCLRE1C):c.*108A>C variant causes a 3 prime UTR 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: DCLRE1C ENST00000378289.8 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.13

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
SUV39H2	NM_001193424.2	c.850-483T>G		intron_variant		ENST00000354919.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUV39H2	ENST00000354919.11	c.850-483T>G		intron_variant		5	NM_001193424.2	P1

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

Gnomad4 AFR exome AF: 0.659

Gnomad4 AMR exome AF: 0.381

Gnomad4 ASJ exome AF: 0.352

Gnomad4 EAS exome AF: 0.469

Gnomad4 SAS exome AF: 0.486

Gnomad4 FIN exome AF: 0.222

Gnomad4 NFE exome AF: 0.287

Gnomad4 OTH exome AF: 0.354

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

Gnomad4 AFR AF: 0.658

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.378

Alfa AF: 0.359 Hom.: 1876

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

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 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

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

Other links and lift over

dbSNP: rs7896464; hg19: chr10-14941055;