rs11594111

Positions:

• chr10-14903407-A-G

Variant summary

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

The NM_001193424.2(SUV39H2):​c.*895A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0948 in 152,262 control chromosomes in the GnomAD database, including 884 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 0.095 (884 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SUV39H2 NM_001193424.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUV39H2	NM_001193424.2	c.*895A>G		3_prime_UTR_variant	6/6	ENST00000354919.11	NP_001180353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUV39H2	ENST00000354919.11	c.*895A>G		3_prime_UTR_variant	6/6	5	NM_001193424.2	ENSP00000346997	P1

Frequencies

GnomAD3 genomes AF: 0.0948 AC: 14429 AN: 152144 Hom.: 884 Cov.: 32

Gnomad AFR AF: 0.0276

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0706

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0810

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.0941

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0948 AC: 14427 AN: 152262 Hom.: 884 Cov.: 32 AF XY: 0.0953 AC XY: 7097 AN XY: 74438

Gnomad4 AFR AF: 0.0276

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.0706

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.0806

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.0945

Alfa AF: 0.123 Hom.: 1582

Bravo AF: 0.0897

Asia WGS AF: 0.0430 AC: 148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11594111; hg19: chr10-14945406;