14-20955631-G-C

Variant names:

• chr14-20955631-G-C
• rs2013109
• NM_002934.3:c.-6+95G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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]

ENSG00000259130 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RNASE2	NM_002934.3	c.-6+95G>C		intron_variant	Intron 1 of 1	ENST00000304625.3	NP_002925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNASE2	ENST00000304625.3	c.-6+95G>C		intron_variant	Intron 1 of 1	1	NM_002934.3	ENSP00000303276.2

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

African (AFR) AF: 0.0760 AC: 1687 AN: 22192

American (AMR) AF: 0.206 AC: 5707 AN: 27670

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 4773 AN: 17444

East Asian (EAS) AF: 0.374 AC: 13878 AN: 37086

South Asian (SAS) AF: 0.314 AC: 18746 AN: 59748

European-Finnish (FIN) AF: 0.209 AC: 9662 AN: 46138

Middle Eastern (MID) AF: 0.249 AC: 729 AN: 2924

European-Non Finnish (NFE) AF: 0.256 AC: 184280 AN: 719358

Other (OTH) AF: 0.249 AC: 10786 AN: 43324

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

African (AFR) AF: 0.0815 AC: 3384 AN: 41516

American (AMR) AF: 0.189 AC: 2885 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 904 AN: 3470

East Asian (EAS) AF: 0.370 AC: 1908 AN: 5150

South Asian (SAS) AF: 0.323 AC: 1558 AN: 4824

European-Finnish (FIN) AF: 0.217 AC: 2289 AN: 10572

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16879 AN: 67972

Other (OTH) AF: 0.213 AC: 451 AN: 2114

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
PhyloP100		0.14
PromoterAI		-0.026	Neutral
Mutation Taster		=100/0	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: rs2013109; hg19: chr14-21423790; COSMIC: COSV58941702;