rs12597040

Variant names:

• chr16-81165950-A-G
• rs12597040
• ENST00000525539.5:c.3107T>C

Your query was ambiguous. Multiple possible variants found:

• chr16-81165950-A-G
• chr16-81165950-A-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4 BP6_Moderate BA1

The ENST00000525539.5(PKD1L2):​c.3107T>C​(p.Leu1036Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,452,888 control chromosomes in the GnomAD database, including 85,572 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (7873 hom., cov: 34)
  • Exomes 𝑓: 0.30 (77699 hom.)
• Consequence: PKD1L2 ENST00000525539.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.284
• Publications: 11 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.11).
• BP6: Variant 16-81165950-A-G is Benign according to our data. Variant chr16-81165950-A-G is described in ClinVar as Benign. ClinVar VariationId is 2788471.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1L2	NR_126532.3	n.3122T>C		non_coding_transcript_exon_variant	Exon 19 of 43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1L2	ENST00000525539.5	c.3107T>C	p.Leu1036Pro	missense_variant	Exon 19 of 43	1		ENSP00000434417.1
PKD1L2	ENST00000533478.5	c.1052T>C	p.Leu351Pro	missense_variant	Exon 8 of 32	1		ENSP00000434644.1
PKD1L2	ENST00000299598.11	n.1436T>C		non_coding_transcript_exon_variant	Exon 10 of 25	5

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46479 AN: 151846 Hom.: 7863 Cov.: 34

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.296

GnomAD2 exomes AF: 0.303 AC: 53998 AN: 178408 AF XY: 0.297

Gnomad AFR exome AF: 0.186

Gnomad AMR exome AF: 0.421

Gnomad ASJ exome AF: 0.141

Gnomad EAS exome AF: 0.664

Gnomad FIN exome AF: 0.323

Gnomad NFE exome AF: 0.232

Gnomad OTH exome AF: 0.253

GnomAD4 exome AF: 0.302 AC: 392509 AN: 1300924 Hom.: 77699 Cov.: 48 AF XY: 0.304 AC XY: 196396 AN XY: 646636

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.194 AC: 5883 AN: 30322

American (AMR) AF: 0.419 AC: 15492 AN: 36970

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 4795 AN: 23830

East Asian (EAS) AF: 0.679 AC: 24594 AN: 36218

South Asian (SAS) AF: 0.421 AC: 30212 AN: 71778

European-Finnish (FIN) AF: 0.348 AC: 17285 AN: 49662

Middle Eastern (MID) AF: 0.227 AC: 1228 AN: 5402

European-Non Finnish (NFE) AF: 0.279 AC: 276486 AN: 992140

Other (OTH) AF: 0.303 AC: 16534 AN: 54602

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.306 AC: 46514 AN: 151964 Hom.: 7873 Cov.: 34 AF XY: 0.315 AC XY: 23365 AN XY: 74258

African (AFR) AF: 0.228 AC: 9472 AN: 41488

American (AMR) AF: 0.371 AC: 5663 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 754 AN: 3456

East Asian (EAS) AF: 0.673 AC: 3447 AN: 5124

South Asian (SAS) AF: 0.456 AC: 2201 AN: 4824

European-Finnish (FIN) AF: 0.364 AC: 3836 AN: 10544

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20093 AN: 67940

Other (OTH) AF: 0.301 AC: 635 AN: 2112

Alfa AF: 0.301 Hom.: 19512

Bravo AF: 0.305

Asia WGS AF: 0.560 AC: 1946 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 01, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.11
CADD	Benign	0.15
DANN	Benign	0.20
PhyloP100		0.28

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: rs12597040; hg19: chr16-81199555; COSMIC: COSV55157719;