Variant chr14-20956082-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000304625.3(RNASE2):c.311A>C(p.Gln104Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000642 in 1,614,252 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00058 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00065 ( 11 hom. )

Consequence

RNASE2
ENST00000304625.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -7.00

Variant links:

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]

RNASE2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007411629).

BP6

Variant 14-20956082-A-C is Benign according to our data. Variant chr14-20956082-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 769856.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNASE2	NM_002934.3 linkuse as main transcript	c.311A>C	p.Gln104Pro	missense_variant	2/2	ENST00000304625.3	NP_002925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNASE2	ENST00000304625.3 linkuse as main transcript	c.311A>C	p.Gln104Pro	missense_variant	2/2	1	NM_002934.3	ENSP00000303276	P1

Frequencies

GnomAD3 genomes

AF:

0.000578

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00641

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00124

AC:

312

AN:

251454

Hom.:

AF XY:

0.00146

AC XY:

199

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00171

Gnomad ASJ exome

AF:

0.00407

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00523

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000404

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000648

AC:

948

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000811

AC XY:

590

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.00165

Gnomad4 ASJ exome

AF:

0.00360

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00548

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000170

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.000578

AC:

AN:

152360

Hom.:

Cov.:

AF XY:

0.000631

AC XY:

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00642

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000524

Hom.:

Bravo

AF:

0.000434

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00124

AC:

151

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.000533

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 12, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.0010

DANN

Benign

0.10

DEOGEN2

Benign

0.0055

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0014

LIST_S2

Benign

0.38

MetaRNN

Benign

0.0074

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.56

MutationTaster

Benign

1.0

PrimateAI

Benign

0.22

PROVEAN

Benign

0.64

REVEL

Benign

0.079

Sift

Benign

0.60

Sift4G

Benign

0.63

Polyphen

0.016

Vest4

0.096

MVP

0.31

MPC

0.49

ClinPred

0.011

GERP RS

-6.0

Varity_R

0.24

gMVP

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over