10-100290091-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016112.3(PKD2L1):ā€‹c.2174T>Cā€‹(p.Val725Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

PKD2L1
NM_016112.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.753
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.123114884).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PKD2L1NM_016112.3 linkc.2174T>C p.Val725Ala missense_variant 14/16 ENST00000318222.4 NP_057196.2 Q9P0L9-1
PKD2L1NM_001253837.2 linkc.2033T>C p.Val678Ala missense_variant 14/16 NP_001240766.1 Q9P0L9Q1L4F0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PKD2L1ENST00000318222.4 linkc.2174T>C p.Val725Ala missense_variant 14/161 NM_016112.3 ENSP00000325296.3 Q9P0L9-1
PKD2L1ENST00000528248.1 linkn.*1914T>C non_coding_transcript_exon_variant 14/161 ENSP00000436514.1 H0YET4
PKD2L1ENST00000528248.1 linkn.*1914T>C 3_prime_UTR_variant 14/161 ENSP00000436514.1 H0YET4
PKD2L1ENST00000465680.2 linkc.104-1613T>C intron_variant 3 ENSP00000434019.1 H0YDN7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461818
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727212
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
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 GeneticsApr 08, 2024The c.2174T>C (p.V725A) alteration is located in exon 14 (coding exon 14) of the PKD2L1 gene. This alteration results from a T to C substitution at nucleotide position 2174, causing the valine (V) at amino acid position 725 to be replaced by an alanine (A). 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
0.096
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
14
DANN
Benign
0.77
DEOGEN2
Benign
0.27
T
Eigen
Benign
-0.77
Eigen_PC
Benign
-0.78
FATHMM_MKL
Benign
0.26
N
LIST_S2
Benign
0.43
T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
1.3
L
PrimateAI
Benign
0.29
T
PROVEAN
Uncertain
-2.6
D
REVEL
Benign
0.062
Sift
Benign
0.19
T
Sift4G
Benign
0.17
T
Polyphen
0.0010
B
Vest4
0.15
MutPred
0.29
Loss of loop (P = 0.0986);
MVP
0.55
MPC
0.080
ClinPred
0.048
T
GERP RS
3.1
Varity_R
0.28
gMVP
0.23

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: chr10-102049848; API