chr7-47800710-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138295.5(PKD1L1):​c.8132G>A​(p.Arg2711Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000308 in 1,614,172 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 (★). Synonymous variant affecting the same amino acid position (i.e. R2711R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

PKD1L1
NM_138295.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: -1.40
Variant links:
Genes affected
PKD1L1 (HGNC:18053): (polycystin 1 like 1, transient receptor potential channel interacting) This gene encodes a member of the polycystin protein family containing 11 transmembrane domains, a receptor for egg jelly (REJ) domain, and a polycystin-1, lipoxygenase, alpha-toxin (PLAT) domain. The encoded protein may play a role in the male reproductive system. Alternative splice variants have been described but their biological nature has not been determined. [provided by RefSeq, Jul 2008]
PKD1L1-AS1 (HGNC:21911): (PKD1L1 antisense RNA 1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.021134675).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PKD1L1NM_138295.5 linkc.8132G>A p.Arg2711Gln missense_variant Exon 54 of 57 ENST00000289672.7 NP_612152.1
PKD1L1XM_017011798.3 linkc.8309G>A p.Arg2770Gln missense_variant Exon 55 of 59 XP_016867287.1
PKD1L1-AS1NR_161268.1 linkn.153+5267C>T intron_variant Intron 1 of 2
PKD1L1-AS1NR_161269.1 linkn.153+5267C>T intron_variant Intron 1 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PKD1L1ENST00000289672.7 linkc.8132G>A p.Arg2711Gln missense_variant Exon 54 of 57 1 NM_138295.5 ENSP00000289672.2 Q8TDX9-1

Frequencies

GnomAD3 genomes
AF:
0.000230
AC:
35
AN:
152164
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000966
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.000326
AC:
82
AN:
251460
Hom.:
0
AF XY:
0.000368
AC XY:
50
AN XY:
135902
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000621
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000325
Gnomad OTH exome
AF:
0.000815
GnomAD4 exome
AF:
0.000316
AC:
462
AN:
1461890
Hom.:
0
Cov.:
32
AF XY:
0.000329
AC XY:
239
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.000209
Gnomad4 AMR exome
AF:
0.000626
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000707
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000280
Gnomad4 OTH exome
AF:
0.000480
GnomAD4 genome
AF:
0.000230
AC:
35
AN:
152282
Hom.:
0
Cov.:
32
AF XY:
0.000215
AC XY:
16
AN XY:
74456
show subpopulations
Gnomad4 AFR
AF:
0.0000963
Gnomad4 AMR
AF:
0.000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000303
Hom.:
0
Bravo
AF:
0.000249
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000264
AC:
32
EpiCase
AF:
0.000545
EpiControl
AF:
0.000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

PKD1L1-related disorder Uncertain:1
Uncertain significance, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesMar 25, 2024The PKD1L1 c.8132G>A variant is predicted to result in the amino acid substitution p.Arg2711Gln. This variant has been previously reported as a variant of uncertain significance in a fetus with complex cardiac malformations and abdominal situs inversus (Patient ID 6610, Supporting Tables S1 and S4, Liu et al. 2020. PubMed ID: 33131162). This variant is reported in 0.062% of alleles in individuals of South Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Heterotaxy, visceral, 8, autosomal Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingBaylor GeneticsJan 19, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Benign
-0.64
T
BayesDel_noAF
Benign
-0.79
CADD
Benign
0.36
DANN
Benign
0.73
DEOGEN2
Benign
0.029
T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.0031
N
LIST_S2
Benign
0.48
T
M_CAP
Benign
0.0014
T
MetaRNN
Benign
0.021
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.34
N
PrimateAI
Benign
0.17
T
PROVEAN
Benign
0.060
N
REVEL
Benign
0.0080
Sift
Benign
0.38
T
Sift4G
Benign
0.38
T
Polyphen
0.086
B
Vest4
0.049
MVP
0.38
MPC
0.11
ClinPred
0.0080
T
GERP RS
-5.5
Varity_R
0.021
gMVP
0.068

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: rs150206836; hg19: chr7-47840308; API