rs7205673

Variant names:

• chr16-81198670-G-A
• rs7205673
• ENST00000525539.5:c.1535C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-81198670-G-A
• chr16-81198670-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000525539.5(PKD1L2):​c.1535C>T​(p.Pro512Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 1,613,156 control chromosomes in the GnomAD database, including 502,089 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P512T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.76 (44155 hom., cov: 32)
  • Exomes 𝑓: 0.79 (457934 hom.)
• Consequence: PKD1L2 ENST00000525539.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66
• Publications: 23 publications found

Genes affected

PKD1L2 (HGNC:21715): (polycystin 1 like 2 (gene/pseudogene)) This gene encodes a member of the polycystin protein family. This protein may function as a G-protein-coupled component or regulator of cation channel pores. The long isoform of this protein contains 11 transmembrane domains, a latrophilin/CL-1-like GPCR proteolytic site (GPS) domain, and a polycystin-1, lipoxygenase, alpha-toxin (PLAT) domain. Alternative splicing results in multiple transcript variants encoding distinct isoforms. This gene is a polymorphic pseudogene in humans. [provided by RefSeq, May 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.383563E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1L2	NR_126532.3	n.1550C>T		non_coding_transcript_exon_variant	Exon 7 of 43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1L2	ENST00000525539.5	c.1535C>T	p.Pro512Leu	missense_variant	Exon 7 of 43	1		ENSP00000434417.1
PKD1L2	ENST00000526632.5	c.116C>T	p.Pro39Leu	missense_variant	Exon 1 of 12	2		ENSP00000436389.1
PKD1L2	ENST00000710634.1	n.149C>T		non_coding_transcript_exon_variant	Exon 1 of 10			ENSP00000518389.1

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115111 AN: 151952 Hom.: 44148 Cov.: 32

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.959

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.742

GnomAD2 exomes AF: 0.791 AC: 196561 AN: 248588 AF XY: 0.790

Gnomad AFR exome AF: 0.644

Gnomad AMR exome AF: 0.795

Gnomad ASJ exome AF: 0.786

Gnomad EAS exome AF: 0.958

Gnomad FIN exome AF: 0.829

Gnomad NFE exome AF: 0.794

Gnomad OTH exome AF: 0.792

GnomAD4 exome AF: 0.790 AC: 1154960 AN: 1461086 Hom.: 457934 Cov.: 68 AF XY: 0.789 AC XY: 573524 AN XY: 726772

African (AFR) AF: 0.649 AC: 21705 AN: 33460

American (AMR) AF: 0.794 AC: 35487 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 20324 AN: 26104

East Asian (EAS) AF: 0.959 AC: 38076 AN: 39694

South Asian (SAS) AF: 0.727 AC: 62610 AN: 86118

European-Finnish (FIN) AF: 0.829 AC: 44247 AN: 53404

Middle Eastern (MID) AF: 0.775 AC: 4257 AN: 5494

European-Non Finnish (NFE) AF: 0.793 AC: 881171 AN: 1111772

Other (OTH) AF: 0.780 AC: 47083 AN: 60336

GnomAD4 genome AF: 0.757 AC: 115148 AN: 152070 Hom.: 44155 Cov.: 32 AF XY: 0.760 AC XY: 56497 AN XY: 74352

African (AFR) AF: 0.655 AC: 27154 AN: 41430

American (AMR) AF: 0.771 AC: 11761 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 2691 AN: 3472

East Asian (EAS) AF: 0.959 AC: 4960 AN: 5170

South Asian (SAS) AF: 0.719 AC: 3467 AN: 4822

European-Finnish (FIN) AF: 0.829 AC: 8786 AN: 10598

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.791 AC: 53817 AN: 67996

Other (OTH) AF: 0.737 AC: 1557 AN: 2112

Alfa AF: 0.785 Hom.: 195940

Bravo AF: 0.754

TwinsUK AF: 0.797 AC: 2955

ALSPAC AF: 0.789 AC: 3040

ESP6500AA AF: 0.664 AC: 2650

ESP6500EA AF: 0.793 AC: 6579

ExAC AF: 0.786 AC: 95012

Asia WGS AF: 0.809 AC: 2812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.53	T
MetaRNN	Benign	9.4e-7	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.7
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.22
Polyphen		1.0	D
Vest4		0.40
ClinPred		0.048	T
GERP RS		5.1
PromoterAI		-0.062	Neutral
Mutation Taster		=86/14	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7205673; hg19: chr16-81232275; COSMIC: COSV107419792;