rs140756661

Variant names:

• chr9-76655459-C-A
• NM_015225.3:c.8320G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-76655459-C-A
• chr9-76655459-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015225.3(PRUNE2):​c.8320G>T​(p.Gly2774Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,616 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G2774S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PRUNE2 NM_015225.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.70

Genes affected

PRUNE2 (HGNC:25209): (prune homolog 2 with BCH domain) The protein encoded by this gene belongs to the B-cell CLL/lymphoma 2 and adenovirus E1B 19 kDa interacting family, whose members play roles in many cellular processes including apotosis, cell transformation, and synaptic function. Several functions for this protein have been demonstrated including suppression of Ras homolog family member A activity, which results in reduced stress fiber formation and suppression of oncogenic cellular transformation. A high molecular weight isoform of this protein has also been shown to colocalize with Adaptor protein complex 2, beta-Adaptin and endodermal markers, suggesting an involvement in post-endocytic trafficking. In prostate cancer cells, this gene acts as a tumor suppressor and its expression is regulated by prostate cancer antigen 3, a non-protein coding gene on the opposite DNA strand in an intron of this gene. Prostate cancer antigen 3 regulates levels of this gene through formation of a double-stranded RNA that undergoes adenosine deaminase actin on RNA-dependent adenosine-to-inosine RNA editing. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

LOC105376095 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3610757).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRUNE2	NM_015225.3	c.8320G>T	p.Gly2774Cys	missense_variant	Exon 10 of 19	ENST00000376718.8	NP_056040.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRUNE2	ENST00000376718.8	c.8320G>T	p.Gly2774Cys	missense_variant	Exon 10 of 19	5	NM_015225.3	ENSP00000365908.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460616 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726426

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.092	.;.;T;T;T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.90	D;D;D;D;D
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.36	T;T;T;T;T
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.3	.;.;M;.;.
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-5.1	D;.;D;.;D
REVEL	Benign	0.19
Sift	Uncertain	0.0040	D;.;D;.;D
Sift4G	Uncertain	0.010	D;D;D;D;D
Polyphen		1.0	.;.;D;.;.
Vest4		0.64
MutPred		0.17		.;.;Loss of catalytic residue at P2770 (P = 0.0711);Loss of catalytic residue at P2770 (P = 0.0711);.;
MVP		0.59
MPC		0.46
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.66
gMVP		0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-79270375;