NM_002934.3:c.-6+106A>C

Variant names:

• chr14-20955642-A-C
• rs10132319
• NM_002934.3:c.-6+106A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002934.3(RNASE2):​c.-6+106A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000898 in 1,113,556 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 9.0e-7 (0 hom.)
• Consequence: RNASE2 NM_002934.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.569
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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>C		intron	N/A	NP_002925.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.98e-7 AC: 1 AN: 1113556 Hom.: 0 Cov.: 15 AF XY: 0.00 AC XY: 0 AN XY: 555912

African (AFR) AF: 0.0000402 AC: 1 AN: 24882

American (AMR) AF: 0.00 AC: 0 AN: 28158

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18234

East Asian (EAS) AF: 0.00 AC: 0 AN: 37800

South Asian (SAS) AF: 0.00 AC: 0 AN: 62748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47868

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3230

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842750

Other (OTH) AF: 0.00 AC: 0 AN: 47886

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.78
DANN	Benign	0.64
PhyloP100		-0.57
PromoterAI		-0.025	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10132319; hg19: chr14-21423801;