16-81207495-G-C

Variant names:

• chr16-81207495-G-C
• rs11150370
• ENST00000525539.5:c.901C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 26 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=1.8343956E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000525539.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1L2	NR_126532.3		n.925C>G		non_coding_transcript_exon	Exon 5 of 43

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1L2	ENST00000525539.5	TSL:1	c.901C>G	p.Pro301Ala	missense	Exon 5 of 43	ENSP00000434417.1

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

GnomAD2 exomes AF: 0.488 AC: 116523 AN: 238748 AF XY: 0.484

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 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

African (AFR) AF: 0.216 AC: 7094 AN: 32804

American (AMR) AF: 0.521 AC: 22168 AN: 42516

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 10513 AN: 25606

East Asian (EAS) AF: 0.841 AC: 32997 AN: 39214

South Asian (SAS) AF: 0.500 AC: 41408 AN: 82762

European-Finnish (FIN) AF: 0.523 AC: 27783 AN: 53160

Middle Eastern (MID) AF: 0.311 AC: 1776 AN: 5710

European-Non Finnish (NFE) AF: 0.473 AC: 521672 AN: 1103644

Other (OTH) AF: 0.471 AC: 28177 AN: 59774

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

African (AFR) AF: 0.225 AC: 9333 AN: 41432

American (AMR) AF: 0.444 AC: 6776 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1455 AN: 3466

East Asian (EAS) AF: 0.847 AC: 4348 AN: 5136

South Asian (SAS) AF: 0.502 AC: 2416 AN: 4810

European-Finnish (FIN) AF: 0.515 AC: 5437 AN: 10558

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31123 AN: 67952

Other (OTH) AF: 0.385 AC: 810 AN: 2102

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
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
PhyloP100		6.1
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
Mutation Taster		=69/31	polymorphism (auto)

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

Other links and lift over

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