rs2013109

chr14-20955631-G-C

Variant summary

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

The NM_002934.3(RNASE2):c.-6+95G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 1,127,990 control chromosomes in the GnomAD database, including 36,899 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 0.20 (3595 hom., cov: 32)
  • Exomes 𝑓: 0.26 (33304 hom.)
• Consequence: RNASE2 NM_002934.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137

Genes affected

RNASE2 (HGNC:10045): (ribonuclease A family member 2) The protein encoded by this gene is a non-secretory ribonuclease that belongs to the pancreatic ribonuclease family, a subset of the ribonuclease A superfamily. The protein antimicrobial activity against viruses. [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNASE2	NM_002934.3	c.-6+95G>C		intron_variant		ENST00000304625.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNASE2	ENST00000304625.3	c.-6+95G>C		intron_variant		1	NM_002934.3	P1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30610 AN: 151988 Hom.: 3595 Cov.: 32

Gnomad AFR AF: 0.0817

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.214

GnomAD4 exome AF: 0.256 AC: 250248 AN: 975884 Hom.: 33304 Cov.: 13 AF XY: 0.258 AC XY: 126989 AN XY: 492384

Gnomad4 AFR exome AF: 0.0760

Gnomad4 AMR exome AF: 0.206

Gnomad4 ASJ exome AF: 0.274

Gnomad4 EAS exome AF: 0.374

Gnomad4 SAS exome AF: 0.314

Gnomad4 FIN exome AF: 0.209

Gnomad4 NFE exome AF: 0.256

Gnomad4 OTH exome AF: 0.249

GnomAD4 genome AF: 0.201 AC: 30612 AN: 152106 Hom.: 3595 Cov.: 32 AF XY: 0.203 AC XY: 15070 AN XY: 74338

Gnomad4 AFR AF: 0.0815

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.370

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.213

Alfa AF: 0.213 Hom.: 474

Bravo AF: 0.197

Asia WGS AF: 0.295 AC: 1026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.3
Dann	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs2013109; hg19: chr14-21423790; COSMIC: COSV58941702;