dbSNP rs12782963: PKD2L1:p.Ala788Val (chr10-100288451-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016112.3(PKD2L1):c.2363C>T(p.Ala788Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict 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: 0.0000021 ( 0 hom. )

Consequence

PKD2L1
NM_016112.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.574

Publications

20 publications found

Variant links:

Genes affected

PKD2L1 (HGNC:9011): (polycystin 2 like 1, transient receptor potential cation channel) This gene encodes a member of the polycystin protein family. The encoded protein contains multiple transmembrane domains, and cytoplasmic N- and C-termini. The protein may be an integral membrane protein involved in cell-cell/matrix interactions. This protein functions as a calcium-regulated nonselective cation channel. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

PKD2L1 links:

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ACMG classification

Classification was made for transcript

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 (MetaRNN=0.05009219).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD2L1	NM_016112.3 link	c.2363C>T	p.Ala788Val	missense_variant	Exon 16 of 16	ENST00000318222.4	NP_057196.2	Q9P0L9-1
PKD2L1	NM_001253837.2 link	c.2222C>T	p.Ala741Val	missense_variant	Exon 16 of 16		NP_001240766.1	Q9P0L9Q1L4F0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PKD2L1	ENST00000318222.4 link	c.2363C>T	p.Ala788Val	missense_variant	Exon 16 of 16	1	NM_016112.3	ENSP00000325296.3	Q9P0L9-1
PKD2L1	ENST00000528248.1 link	n.*2103C>T		non_coding_transcript_exon_variant	Exon 16 of 16	1		ENSP00000436514.1	H0YET4
PKD2L1	ENST00000528248.1 link	n.*2103C>T		3_prime_UTR_variant	Exon 16 of 16	1		ENSP00000436514.1	H0YET4
PKD2L1	ENST00000465680.2 link	c.131C>T	p.Ala44Val	missense_variant	Exon 2 of 2	3		ENSP00000434019.1	H0YDN7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251146

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00000206

AC:

AN:

1459422

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726242

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33400

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86196

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109810

Other (OTH)

AF:

0.00

AC:

AN:

60314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.51

CADD

Benign

4.3

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.019

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.45

M_CAP

Benign

0.014

MetaRNN

Benign

0.050

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.55

PhyloP100

-0.57

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.54

REVEL

Benign

0.10

Sift

Pathogenic

0.0

Sift4G

Benign

0.30

Polyphen

0.0010

Vest4

0.097

MutPred

0.20

Gain of catalytic residue at A788 (P = 0.0186);

MVP

0.42

MPC

0.20

ClinPred

0.12

GERP RS

-1.1

Varity_R

0.073

gMVP

0.25

Mutation Taster

=95/5

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over