6-166929583-GGGCATCAATGCTT-G

Variant names:

• chr6-166929583-GGGCATCAATGCTT-G
• NM_003730.6:c.763_*4delAAGCATTGATGCC

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_003730.6(RNASET2):​c.763_*4delAAGCATTGATGCC​(p.Lys255fs) variant causes a frameshift, stop lost change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. K255K) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RNASET2 NM_003730.6 frameshift, stop_lost
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.68

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]

ENSG00000249141 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Stoplost variant. No alternative stopcodon identified downstream, so we assume a Nonstop Mediated Decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASET2	NM_003730.6	c.763_*4delAAGCATTGATGCC	p.Lys255fs	frameshift_variant, stop_lost	Exon 9 of 9	ENST00000508775.6	NP_003721.2
RNASET2	NM_003730.6	c.762_*4delAAGCATTGATGCC		3_prime_UTR_variant	Exon 9 of 9	ENST00000508775.6	NP_003721.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNASET2	ENST00000508775.6	c.763_*4delAAGCATTGATGCC	p.Lys255fs	frameshift_variant, stop_lost	Exon 9 of 9	1	NM_003730.6	ENSP00000426455.2
RNASET2	ENST00000508775	c.762_*4delAAGCATTGATGCC		3_prime_UTR_variant	Exon 9 of 9	1	NM_003730.6	ENSP00000426455.2
ENSG00000249141	ENST00000507747.1	c.432+4495_432+4507delAAGCATTGATGCC		intron_variant	Intron 7 of 7	5		ENSP00000426906.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Dec 02, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This sequence change results in a frameshift in the RNASET2 gene (p.Lys255Glnfs*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 2 amino acid(s) of the RNASET2 protein and extend the protein by 20 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RNASET2-related conditions. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-167343071;