rs10132319

Positions:

• chr14-20955642-A-G

Variant summary

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

The NM_002934.3(RNASE2):​c.-6+106A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.018 in 1,265,762 control chromosomes in the GnomAD database, including 1,280 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 0.058 (696 hom., cov: 32)
  • Exomes 𝑓: 0.013 (584 hom.)
• Consequence: RNASE2 NM_002934.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.569

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNASE2	NM_002934.3	c.-6+106A>G		intron_variant		ENST00000304625.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNASE2	ENST00000304625.3	c.-6+106A>G		intron_variant		1	NM_002934.3	P1

Frequencies

GnomAD3 genomes AF: 0.0578 AC: 8796 AN: 152158 Hom.: 691 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0199

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.0973

Gnomad SAS AF: 0.0261

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00517

Gnomad OTH AF: 0.0406

GnomAD4 exome AF: 0.0125 AC: 13946 AN: 1113486 Hom.: 584 Cov.: 15 AF XY: 0.0124 AC XY: 6883 AN XY: 555872

Gnomad4 AFR exome AF: 0.178

Gnomad4 AMR exome AF: 0.0132

Gnomad4 ASJ exome AF: 0.00494

Gnomad4 EAS exome AF: 0.0677

Gnomad4 SAS exome AF: 0.0266

Gnomad4 FIN exome AF: 0.000731

Gnomad4 NFE exome AF: 0.00455

Gnomad4 OTH exome AF: 0.0186

GnomAD4 genome AF: 0.0579 AC: 8821 AN: 152276 Hom.: 696 Cov.: 32 AF XY: 0.0563 AC XY: 4196 AN XY: 74468

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.0199

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.0971

Gnomad4 SAS AF: 0.0257

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00516

Gnomad4 OTH AF: 0.0406

Alfa AF: 0.0226 Hom.: 108

Bravo AF: 0.0650

Asia WGS AF: 0.0640 AC: 220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.90
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs10132319; hg19: chr14-21423801;