Variant 10-100290485-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_016112.3(PKD2L1):c.2042G>A(p.Arg681Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,461,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict 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. R681L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

PKD2L1
NM_016112.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.29

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKD2L1	NM_016112.3 linkuse as main transcript	c.2042G>A	p.Arg681Gln	missense_variant	13/16	ENST00000318222.4	NP_057196.2	Q9P0L9-1
PKD2L1	NM_001253837.2 linkuse as main transcript	c.1901G>A	p.Arg634Gln	missense_variant	13/16		NP_001240766.1	Q9P0L9Q1L4F0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PKD2L1	ENST00000318222.4 linkuse as main transcript	c.2042G>A	p.Arg681Gln	missense_variant	13/16	1	NM_016112.3	ENSP00000325296.3	Q9P0L9-1
PKD2L1	ENST00000528248.1 linkuse as main transcript	n.*1782G>A		non_coding_transcript_exon_variant	13/16	1		ENSP00000436514.1	H0YET4
PKD2L1	ENST00000528248.1 linkuse as main transcript	n.*1782G>A		3_prime_UTR_variant	13/16	1		ENSP00000436514.1	H0YET4
PKD2L1	ENST00000465680.2 linkuse as main transcript	c.104-2007G>A		intron_variant		3		ENSP00000434019.1	H0YDN7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000799

AC:

AN:

250460

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135478

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 SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1461072

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726896

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.052

DANN

Benign

0.92

DEOGEN2

Benign

0.029

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0065

LIST_S2

Benign

0.71

M_CAP

Benign

0.015

MetaRNN

Benign

0.029

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.17

PrimateAI

Benign

0.18

PROVEAN

Benign

-1.4

REVEL

Benign

0.14

Sift

Benign

0.26

Sift4G

Benign

0.31

Polyphen

0.0030

Vest4

0.038

MutPred

0.28

Loss of MoRF binding (P = 0.0198);

MVP

0.23

MPC

0.077

ClinPred

0.095

GERP RS

-6.2

Varity_R

0.045

gMVP

0.077

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.21

Position offset: 34

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over