chr10-100290125-C-A
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM1PP3BS2
The NM_016112.3(PKD2L1):c.2140G>T(p.Val714Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000136 in 1,614,042 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 1 hom. )
Consequence
PKD2L1
NM_016112.3 missense
NM_016112.3 missense
Scores
6
10
3
Clinical Significance
Conservation
PhyloP100: 7.01
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PM1
?
In a mutagenesis_site Abolishes homooligomer formation; when associated with A-710; A-717; A-728; A-731 and A-735. (size 0) in uniprot entity PK2L1_HUMAN
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.801
BS2
?
High AC in GnomAd at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PKD2L1 | NM_016112.3 | c.2140G>T | p.Val714Phe | missense_variant | 14/16 | ENST00000318222.4 | |
PKD2L1 | NM_001253837.2 | c.1999G>T | p.Val667Phe | missense_variant | 14/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PKD2L1 | ENST00000318222.4 | c.2140G>T | p.Val714Phe | missense_variant | 14/16 | 1 | NM_016112.3 | P1 | |
PKD2L1 | ENST00000528248.1 | c.*1880G>T | 3_prime_UTR_variant, NMD_transcript_variant | 14/16 | 1 | ||||
PKD2L1 | ENST00000465680.2 | c.105-1647G>T | intron_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152186Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251354Hom.: 1 AF XY: 0.0000221 AC XY: 3AN XY: 135840
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GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461856Hom.: 1 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727232
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74344
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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 submitter | clinical testing | Ambry Genetics | Nov 03, 2023 | The c.2140G>T (p.V714F) alteration is located in exon 14 (coding exon 14) of the PKD2L1 gene. This alteration results from a G to T substitution at nucleotide position 2140, causing the valine (V) at amino acid position 714 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of sheet (P = 0.0125);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at