16-81207495-G-C

Position:

• chr16-81207495-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000525539.5(PKD1L2):​c.901C>G​(p.Pro301Ala) variant causes a missense change. The variant allele was found at a frequency of 0.473 in 1,597,098 control chromosomes in the GnomAD database, including 186,435 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. P301L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.41 (14267 hom., cov: 31)
  • Exomes 𝑓: 0.48 (172168 hom.)
• Consequence: PKD1L2 ENST00000525539.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.15

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.8343956E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKD1L2	NR_126532.3	n.925C>G		non_coding_transcript_exon_variant	5/43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKD1L2	ENST00000525539.5	c.901C>G	p.Pro301Ala	missense_variant	5/43	1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62161 AN: 151788 Hom.: 14259 Cov.: 31

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.385

GnomAD3 exomes AF: 0.488 AC: 116523 AN: 238748 Hom.: 30771 AF XY: 0.484 AC XY: 62732 AN XY: 129500

Gnomad AFR exome AF: 0.217

Gnomad AMR exome AF: 0.536

Gnomad ASJ exome AF: 0.409

Gnomad EAS exome AF: 0.853

Gnomad SAS exome AF: 0.501

Gnomad FIN exome AF: 0.519

Gnomad NFE exome AF: 0.452

Gnomad OTH exome AF: 0.454

GnomAD4 exome AF: 0.480 AC: 693588 AN: 1445190 Hom.: 172168 Cov.: 39 AF XY: 0.479 AC XY: 344243 AN XY: 717946

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.521

Gnomad4 ASJ exome AF: 0.411

Gnomad4 EAS exome AF: 0.841

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.523

Gnomad4 NFE exome AF: 0.473

Gnomad4 OTH exome AF: 0.471

GnomAD4 genome AF: 0.410 AC: 62208 AN: 151908 Hom.: 14267 Cov.: 31 AF XY: 0.416 AC XY: 30916 AN XY: 74232

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.847

Gnomad4 SAS AF: 0.502

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.385

Alfa AF: 0.404 Hom.: 4011

Bravo AF: 0.400

TwinsUK AF: 0.482 AC: 1786

ALSPAC AF: 0.474 AC: 1827

ESP6500AA AF: 0.207 AC: 788

ESP6500EA AF: 0.427 AC: 3522

ExAC AF: 0.481 AC: 58165

Asia WGS AF: 0.654 AC: 2270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.53	T
MetaRNN	Benign	0.0000018	T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	0.59	P
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Uncertain	0.37
Polyphen		0.95	P
Vest4		0.58
ClinPred		0.025	T
GERP RS		4.9

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

Other links and lift over

dbSNP: rs11150370; hg19: chr16-81241100; COSMIC: COSV61412134;