chr10-100291345-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_016112.3(PKD2L1):​c.1963G>A​(p.Glu655Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 0.0000055 ( 0 hom. )

Consequence

PKD2L1
NM_016112.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.527
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.09138304).
BS2
High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PKD2L1NM_016112.3 linkuse as main transcriptc.1963G>A p.Glu655Lys missense_variant 12/16 ENST00000318222.4 NP_057196.2 Q9P0L9-1
PKD2L1NM_001253837.2 linkuse as main transcriptc.1822G>A p.Glu608Lys missense_variant 12/16 NP_001240766.1 Q9P0L9Q1L4F0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PKD2L1ENST00000318222.4 linkuse as main transcriptc.1963G>A p.Glu655Lys missense_variant 12/161 NM_016112.3 ENSP00000325296.3 Q9P0L9-1
PKD2L1ENST00000528248.1 linkuse as main transcriptn.*1703G>A non_coding_transcript_exon_variant 12/161 ENSP00000436514.1 H0YET4
PKD2L1ENST00000528248.1 linkuse as main transcriptn.*1703G>A 3_prime_UTR_variant 12/161 ENSP00000436514.1 H0YET4
PKD2L1ENST00000465680.2 linkuse as main transcriptc.104-2867G>A intron_variant 3 ENSP00000434019.1 H0YDN7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251448
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135900
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461826
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
727216
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 10, 2024The c.1963G>A (p.E655K) alteration is located in exon 12 (coding exon 12) of the PKD2L1 gene. This alteration results from a G to A substitution at nucleotide position 1963, causing the glutamic acid (E) at amino acid position 655 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.062
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
15
DANN
Benign
0.96
DEOGEN2
Benign
0.10
T
Eigen
Benign
-0.81
Eigen_PC
Benign
-0.70
FATHMM_MKL
Benign
0.70
D
LIST_S2
Benign
0.78
T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.091
T
MetaSVM
Benign
-0.77
T
MutationAssessor
Benign
1.5
L
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.18
Sift
Benign
0.14
T
Sift4G
Benign
0.13
T
Polyphen
0.0050
B
Vest4
0.22
MutPred
0.42
Gain of MoRF binding (P = 0.0061);
MVP
0.47
MPC
0.076
ClinPred
0.11
T
GERP RS
1.8
Varity_R
0.039
gMVP
0.24

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

LitVar

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

Other links and lift over

dbSNP: rs1439283507; hg19: chr10-102051102; API