rs2236313

Variant names:

• chr6-166946901-T-C
• rs2236313
• NM_003730.6:c.204-162A>G

Variant summary

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

The NM_003730.6(RNASET2):​c.204-162A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 691,096 control chromosomes in the GnomAD database, including 84,511 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 0.50 (19706 hom., cov: 32)
  • Exomes 𝑓: 0.48 (64805 hom.)
• Consequence: RNASET2 NM_003730.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233
• Publications: 48 publications found

Genes affected

RNASET2 (HGNC:21686): (ribonuclease T2) This ribonuclease gene is a novel member of the Rh/T2/S-glycoprotein class of extracellular ribonucleases. It is a single copy gene that maps to 6q27, a region associated with human malignancies and chromosomal rearrangement. [provided by RefSeq, Jul 2008]

RNASET2 Gene-Disease associations (from GenCC):

• cystic leukoencephalopathy without megalencephaly

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Orphanet, Illumina

ENSG00000249141 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003730.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASET2	NM_003730.6	MANE Select	c.204-162A>G		intron	N/A	NP_003721.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASET2	ENST00000508775.6	TSL:1 MANE Select	c.204-162A>G		intron	N/A	ENSP00000426455.2	O00584-1
	ENSG00000249141	ENST00000507747.1	TSL:5	c.144-162A>G		intron	N/A	ENSP00000426906.1	H0YAE9
	RNASET2	ENST00000870284.1		c.204-162A>G		intron	N/A	ENSP00000540343.1

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76057 AN: 151910 Hom.: 19674 Cov.: 32

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.520

GnomAD2 exomes AF: 0.528 AC: 70751 AN: 133926 AF XY: 0.530

Gnomad AFR exome AF: 0.598

Gnomad AMR exome AF: 0.643

Gnomad ASJ exome AF: 0.509

Gnomad EAS exome AF: 0.631

Gnomad FIN exome AF: 0.457

Gnomad NFE exome AF: 0.415

Gnomad OTH exome AF: 0.512

GnomAD4 exome AF: 0.479 AC: 258327 AN: 539068 Hom.: 64805 Cov.: 4 AF XY: 0.487 AC XY: 142055 AN XY: 291858

African (AFR) AF: 0.587 AC: 8650 AN: 14734

American (AMR) AF: 0.639 AC: 20606 AN: 32232

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 9929 AN: 19418

East Asian (EAS) AF: 0.606 AC: 19061 AN: 31478

South Asian (SAS) AF: 0.656 AC: 39039 AN: 59524

European-Finnish (FIN) AF: 0.451 AC: 17580 AN: 38996

Middle Eastern (MID) AF: 0.499 AC: 1452 AN: 2912

European-Non Finnish (NFE) AF: 0.412 AC: 127703 AN: 310150

Other (OTH) AF: 0.483 AC: 14307 AN: 29624

GnomAD4 genome AF: 0.501 AC: 76143 AN: 152028 Hom.: 19706 Cov.: 32 AF XY: 0.508 AC XY: 37741 AN XY: 74334

African (AFR) AF: 0.586 AC: 24288 AN: 41436

American (AMR) AF: 0.577 AC: 8819 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1769 AN: 3470

East Asian (EAS) AF: 0.621 AC: 3214 AN: 5176

South Asian (SAS) AF: 0.662 AC: 3185 AN: 4810

European-Finnish (FIN) AF: 0.454 AC: 4792 AN: 10560

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28307 AN: 67970

Other (OTH) AF: 0.525 AC: 1110 AN: 2114

Alfa AF: 0.448 Hom.: 71978

Bravo AF: 0.515

Asia WGS AF: 0.650 AC: 2260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.99
DANN	Benign	0.47
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2236313; hg19: chr6-167360389; COSMIC: COSV107213291; COSMIC: COSV107213291;