chr7-47800710-C-T

Variant names:

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

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 links:

PKD1L1-AS1 (HGNC:21911): (PKD1L1 antisense RNA 1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

PKD1L1-AS1 links:

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
PKD1L1	NM_138295.5 link	c.8132G>A	p.Arg2711Gln	missense_variant	Exon 54 of 57	ENST00000289672.7	NP_612152.1
PKD1L1	XM_017011798.3 link	c.8309G>A	p.Arg2770Gln	missense_variant	Exon 55 of 59		XP_016867287.1
PKD1L1-AS1	NR_161268.1 link	n.153+5267C>T		intron_variant	Intron 1 of 2
PKD1L1-AS1	NR_161269.1 link	n.153+5267C>T		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1L1	ENST00000289672.7 link	c.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:

AN:

152164

Hom.:

Cov.:

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:

AN:

251460

Hom.:

AF XY:

0.000368

AC XY:

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.:

Cov.:

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:

AN:

152282

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

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.:

Bravo

AF:

0.000249

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000264

AC:

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

Mar 25, 2024

PreventionGenetics, part of Exact Sciences

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

The 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

Jan 19, 2024

Baylor Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.36

DANN

Benign

0.73

DEOGEN2

Benign

0.029

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0031

LIST_S2

Benign

0.48

M_CAP

Benign

0.0014

MetaRNN

Benign

0.021

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

PrimateAI

Benign

0.17

PROVEAN

Benign

0.060

REVEL

Benign

0.0080

Sift

Benign

0.38

Sift4G

Benign

0.38

Polyphen

0.086

Vest4

0.049

MVP

0.38

MPC

0.11

ClinPred

0.0080

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over