Genetic Variant NM_002934.3:c.-6+106A>G (chr14-20955642-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.569

Publications

4 publications found

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:

ENSG00000259130 (HGNC:):

ENSG00000259130 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002934.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASE2	NM_002934.3	MANE Select	c.-6+106A>G		intron	N/A	NP_002925.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RNASE2	ENST00000304625.3	TSL:1 MANE Select	c.-6+106A>G	intron	N/A	ENSP00000303276.2
ENSG00000259130	ENST00000717680.1		n.346+21982T>C	intron	N/A
ENSG00000259130	ENST00000796665.1		n.772+15964T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0578

AC:

8796

AN:

152158

Hom.:

691

Cov.:

show subpopulations

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.:

AF XY:

0.0124

AC XY:

6883

AN XY:

555872

show subpopulations

African (AFR)

AF:

0.178

AC:

4436

AN:

24860

American (AMR)

AF:

0.0132

AC:

371

AN:

28158

Ashkenazi Jewish (ASJ)

AF:

0.00494

AC:

AN:

18234

East Asian (EAS)

AF:

0.0677

AC:

2557

AN:

37796

South Asian (SAS)

AF:

0.0266

AC:

1672

AN:

62744

European-Finnish (FIN)

AF:

0.000731

AC:

AN:

47868

Middle Eastern (MID)

AF:

0.0173

AC:

AN:

3230

European-Non Finnish (NFE)

AF:

0.00455

AC:

3838

AN:

842712

Other (OTH)

AF:

0.0186

AC:

891

AN:

47884

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

657

1314

1970

2627

3284

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

268

536

804

1072

1340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0579

AC:

8821

AN:

152276

Hom.:

696

Cov.:

AF XY:

0.0563

AC XY:

4196

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.179

AC:

7424

AN:

41530

American (AMR)

AF:

0.0199

AC:

304

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3472

East Asian (EAS)

AF:

0.0971

AC:

503

AN:

5178

South Asian (SAS)

AF:

0.0257

AC:

124

AN:

4828

European-Finnish (FIN)

AF:

0.000565

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00516

AC:

351

AN:

68016

Other (OTH)

AF:

0.0406

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

375

750

1126

1501

1876

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0263

Hom.:

151

Bravo

AF:

0.0650

Asia WGS

AF:

0.0640

AC:

220

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.90

(source)

DANN

Benign

0.65

PhyloP100

-0.57

PromoterAI

-0.0037

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over