rs11594111

Variant names:

• chr10-14903407-A-G
• rs11594111
• ENST00000378331.5:n.*1844A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000378331.5(SUV39H2):​n.*1844A>G variant causes a non coding transcript exon 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 ENST00000378331.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289
• Publications: 19 publications found

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]

DCLRE1C Gene-Disease associations (from GenCC):

• Omenn syndrome

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: G2P, Ambry Genetics, Orphanet
• severe combined immunodeficiency due to DCLRE1C deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SUV39H2	NM_001193424.2	c.*895A>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000354919.11	NP_001180353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUV39H2	ENST00000354919.11	c.*895A>G		3_prime_UTR_variant	Exon 6 of 6	5	NM_001193424.2	ENSP00000346997.6

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0276 AC: 1147 AN: 41590

American (AMR) AF: 0.107 AC: 1641 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0706 AC: 245 AN: 3470

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5182

South Asian (SAS) AF: 0.0806 AC: 389 AN: 4826

European-Finnish (FIN) AF: 0.137 AC: 1449 AN: 10578

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9222 AN: 68002

Other (OTH) AF: 0.0945 AC: 200 AN: 2116

Alfa AF: 0.122 Hom.: 1848

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
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11594111; hg19: chr10-14945406;