10-14898695-C-T

Variant names:

• chr10-14898695-C-T
• rs7907802
• ENST00000378289:c.*469G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001350965.2(DCLRE1C):​c.*555G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,086 control chromosomes in the GnomAD database, including 7,321 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (7318 hom., cov: 31)
  • Exomes 𝑓: 0.15 (3 hom.)
• Consequence: DCLRE1C NM_001350965.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUV39H2	NM_001193424.2	c.850-844C>T		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.850-844C>T		intron_variant	Intron 3 of 5	5	NM_001193424.2	ENSP00000346997.6

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39942 AN: 151810 Hom.: 7283 Cov.: 31

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.0784

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.239

GnomAD4 exome AF: 0.146 AC: 23 AN: 158 Hom.: 3 Cov.: 0 AF XY: 0.146 AC XY: 12 AN XY: 82

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0952

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.264 AC: 40040 AN: 151928 Hom.: 7318 Cov.: 31 AF XY: 0.266 AC XY: 19772 AN XY: 74258

Gnomad4 AFR AF: 0.500

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.258

Gnomad4 EAS AF: 0.412

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.0784

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.237

Alfa AF: 0.175 Hom.: 2979

Bravo AF: 0.285

Asia WGS AF: 0.359 AC: 1247 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.5
DANN	Benign	0.70

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: rs7907802; hg19: chr10-14940694;