Genetic Variant PKD2L2:p.Ile287Val (chr5-137906318-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001300921.2(PKD2L2):c.859A>G(p.Ile287Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,455,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PKD2L2
NM_001300921.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.977

Publications

0 publications found

Variant links:

Genes affected

PKD2L2 (HGNC:9012): (polycystin 2 like 2, transient receptor potential cation channel) Predicted to enable calcium channel activity. Predicted to be involved in detection of mechanical stimulus. Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

PKD2L2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.112811685).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300921.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PKD2L2	NM_001300921.2	MANE Select	c.859A>G	p.Ile287Val	missense	Exon 6 of 15	NP_001287850.1	Q9NZM6-1
PKD2L2	NM_014386.4		c.859A>G	p.Ile287Val	missense	Exon 6 of 14	NP_055201.2	Q9NZM6-5
PKD2L2	NM_001258448.2		c.859A>G	p.Ile287Val	missense	Exon 6 of 15	NP_001245377.1	Q9NZM6-7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PKD2L2	ENST00000508883.6	TSL:1 MANE Select	c.859A>G	p.Ile287Val	missense	Exon 6 of 15	ENSP00000424725.1	Q9NZM6-1
PKD2L2	ENST00000290431.5	TSL:1	c.859A>G	p.Ile287Val	missense	Exon 6 of 14	ENSP00000290431.5	Q9NZM6-5
PKD2L2	ENST00000508638.5	TSL:1	c.859A>G	p.Ile287Val	missense	Exon 6 of 13	ENSP00000423382.1	Q9NZM6-6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249310

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1455784

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724598

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33350

American (AMR)

AF:

0.00

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26090

East Asian (EAS)

AF:

0.00

AC:

AN:

39624

South Asian (SAS)

AF:

0.00

AC:

AN:

86088

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

9.04e-7

AC:

AN:

1106634

Other (OTH)

AF:

0.00

AC:

AN:

60162

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.090

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.74

M_CAP

Benign

0.012

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.11

PhyloP100

0.98

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.020

REVEL

Benign

0.034

Sift

Benign

0.50

Sift4G

Benign

0.80

Polyphen

0.0020

Vest4

0.14

MutPred

0.45

Gain of catalytic residue at I287 (P = 0.0411)

MVP

0.62

MPC

0.17

ClinPred

0.041

GERP RS

1.5

Varity_R

0.055

gMVP

0.31

Mutation Taster

=88/12

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over