chr10-100288512-G-A

Variant names:

• chr10-100288512-G-A
• rs2305386
• NM_016112.3:c.2336-34C>T

Variant summary

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

The NM_016112.3(PKD2L1):​c.2336-34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0478 in 1,306,946 control chromosomes in the GnomAD database, including 1,692 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.

• Frequency:
  • Genomes: 𝑓 0.063 (340 hom., cov: 32)
  • Exomes 𝑓: 0.046 (1352 hom.)
• Consequence: PKD2L1 NM_016112.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.821
• Publications: 10 publications found

Genes affected

PKD2L1 (HGNC:9011): (polycystin 2 like 1, transient receptor potential cation channel) This gene encodes a member of the polycystin protein family. The encoded protein contains multiple transmembrane domains, and cytoplasmic N- and C-termini. The protein may be an integral membrane protein involved in cell-cell/matrix interactions. This protein functions as a calcium-regulated nonselective cation channel. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD2L1	NM_016112.3	c.2336-34C>T		intron_variant	Intron 15 of 15	ENST00000318222.4	NP_057196.2
PKD2L1	NM_001253837.2	c.2195-34C>T		intron_variant	Intron 15 of 15		NP_001240766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD2L1	ENST00000318222.4	c.2336-34C>T		intron_variant	Intron 15 of 15	1	NM_016112.3	ENSP00000325296.3
PKD2L1	ENST00000528248.1	n.*2076-34C>T		intron_variant	Intron 15 of 15	1		ENSP00000436514.1
PKD2L1	ENST00000465680.2	c.104-34C>T		intron_variant	Intron 1 of 1	3		ENSP00000434019.1

Frequencies

GnomAD3 genomes AF: 0.0627 AC: 9532 AN: 152058 Hom.: 340 Cov.: 32

Gnomad AFR AF: 0.0952

Gnomad AMI AF: 0.0736

Gnomad AMR AF: 0.0491

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.0554

Gnomad SAS AF: 0.0644

Gnomad FIN AF: 0.0557

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0472

Gnomad OTH AF: 0.0670

GnomAD2 exomes AF: 0.0517 AC: 12820 AN: 248012 AF XY: 0.0511

Gnomad AFR exome AF: 0.0976

Gnomad AMR exome AF: 0.0445

Gnomad ASJ exome AF: 0.0636

Gnomad EAS exome AF: 0.0521

Gnomad FIN exome AF: 0.0494

Gnomad NFE exome AF: 0.0440

Gnomad OTH exome AF: 0.0506

GnomAD4 exome AF: 0.0459 AC: 52975 AN: 1154770 Hom.: 1352 Cov.: 16 AF XY: 0.0463 AC XY: 27289 AN XY: 589194

African (AFR) AF: 0.0897 AC: 2445 AN: 27250

American (AMR) AF: 0.0451 AC: 1992 AN: 44168

Ashkenazi Jewish (ASJ) AF: 0.0605 AC: 1466 AN: 24228

East Asian (EAS) AF: 0.0643 AC: 2466 AN: 38352

South Asian (SAS) AF: 0.0564 AC: 4512 AN: 79998

European-Finnish (FIN) AF: 0.0515 AC: 2730 AN: 53052

Middle Eastern (MID) AF: 0.0473 AC: 248 AN: 5238

European-Non Finnish (NFE) AF: 0.0413 AC: 34411 AN: 832334

Other (OTH) AF: 0.0539 AC: 2705 AN: 50150

GnomAD4 genome AF: 0.0627 AC: 9539 AN: 152176 Hom.: 340 Cov.: 32 AF XY: 0.0630 AC XY: 4689 AN XY: 74400

African (AFR) AF: 0.0950 AC: 3947 AN: 41526

American (AMR) AF: 0.0491 AC: 751 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0657 AC: 228 AN: 3468

East Asian (EAS) AF: 0.0557 AC: 288 AN: 5170

South Asian (SAS) AF: 0.0642 AC: 309 AN: 4812

European-Finnish (FIN) AF: 0.0557 AC: 590 AN: 10592

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0472 AC: 3209 AN: 68012

Other (OTH) AF: 0.0663 AC: 140 AN: 2112

Alfa AF: 0.0565 Hom.: 71

Bravo AF: 0.0636

Asia WGS AF: 0.0810 AC: 282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.3
DANN	Benign	0.46
PhyloP100		0.82
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2305386; hg19: chr10-102048269; COSMIC: COSV58396704; COSMIC: COSV58396704;