rs17353856

Variant names:

• chr10-14899655-C-T
• rs17353856
• NM_001193424.2:c.966C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP7 BA1

The NM_001193424.2(SUV39H2):​c.966C>T​(p.Tyr322Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,613,652 control chromosomes in the GnomAD database, including 13,659 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.095 (882 hom., cov: 32)
  • Exomes 𝑓: 0.13 (12777 hom.)
• Consequence: SUV39H2 NM_001193424.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.128
• Publications: 26 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 -9 ACMG points.

• BP7: Synonymous conserved (PhyloP=0.128 with no splicing effect.
• 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.966C>T	p.Tyr322Tyr	synonymous_variant	Exon 4 of 6	ENST00000354919.11	NP_001180353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUV39H2	ENST00000354919.11	c.966C>T	p.Tyr322Tyr	synonymous_variant	Exon 4 of 6	5	NM_001193424.2	ENSP00000346997.6

Frequencies

GnomAD3 genomes AF: 0.0954 AC: 14515 AN: 152096 Hom.: 882 Cov.: 32

Gnomad AFR AF: 0.0311

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0706

Gnomad EAS AF: 0.00288

Gnomad SAS AF: 0.0813

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.0957

GnomAD2 exomes AF: 0.105 AC: 26228 AN: 250970 AF XY: 0.105

Gnomad AFR exome AF: 0.0291

Gnomad AMR exome AF: 0.114

Gnomad ASJ exome AF: 0.0708

Gnomad EAS exome AF: 0.00245

Gnomad FIN exome AF: 0.126

Gnomad NFE exome AF: 0.133

Gnomad OTH exome AF: 0.0996

GnomAD4 exome AF: 0.128 AC: 186402 AN: 1461438 Hom.: 12777 Cov.: 32 AF XY: 0.126 AC XY: 91663 AN XY: 727000

African (AFR) AF: 0.0274 AC: 918 AN: 33466

American (AMR) AF: 0.114 AC: 5083 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.0673 AC: 1759 AN: 26124

East Asian (EAS) AF: 0.00224 AC: 89 AN: 39690

South Asian (SAS) AF: 0.0882 AC: 7599 AN: 86160

European-Finnish (FIN) AF: 0.125 AC: 6666 AN: 53400

Middle Eastern (MID) AF: 0.111 AC: 642 AN: 5768

European-Non Finnish (NFE) AF: 0.141 AC: 156696 AN: 1111798

Other (OTH) AF: 0.115 AC: 6950 AN: 60376

GnomAD4 genome AF: 0.0953 AC: 14512 AN: 152214 Hom.: 882 Cov.: 32 AF XY: 0.0957 AC XY: 7124 AN XY: 74406

African (AFR) AF: 0.0310 AC: 1288 AN: 41534

American (AMR) AF: 0.105 AC: 1604 AN: 15292

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

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5192

South Asian (SAS) AF: 0.0809 AC: 390 AN: 4820

European-Finnish (FIN) AF: 0.137 AC: 1447 AN: 10572

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

European-Non Finnish (NFE) AF: 0.135 AC: 9202 AN: 68016

Other (OTH) AF: 0.0961 AC: 203 AN: 2112

Alfa AF: 0.113 Hom.: 1128

Bravo AF: 0.0899

Asia WGS AF: 0.0430 AC: 149 AN: 3478

EpiCase AF: 0.129

EpiControl AF: 0.128

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	5.7
DANN	Benign	0.89
PhyloP100		0.13
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=90/10	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17353856; hg19: chr10-14941654;