10-100315722-G-A

Position:

• chr10-100315722-G-A

Variant summary

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

The ENST00000318222.4(PKD2L1):​c.349+13489C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,012 control chromosomes in the GnomAD database, including 12,219 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 0.33 (12219 hom., cov: 32)
• Consequence: PKD2L1 ENST00000318222.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.640

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKD2L1	NM_016112.3	c.349+13489C>T		intron_variant		ENST00000318222.4	NP_057196.2
PKD2L1	NM_001253837.2	c.208+13489C>T		intron_variant			NP_001240766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKD2L1	ENST00000318222.4	c.349+13489C>T		intron_variant		1	NM_016112.3	ENSP00000325296	P1
PKD2L1	ENST00000528248.1	c.*89+13489C>T		intron_variant, NMD_transcript_variant		1		ENSP00000436514
PKD2L1	ENST00000465680.2	c.104+14147C>T		intron_variant		3		ENSP00000434019
PKD2L1	ENST00000532547.1	c.*93+13489C>T		intron_variant, NMD_transcript_variant		4		ENSP00000434224

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49945 AN: 151894 Hom.: 12177 Cov.: 32

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.0702

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.341

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.329 AC: 50041 AN: 152012 Hom.: 12219 Cov.: 32 AF XY: 0.325 AC XY: 24154 AN XY: 74314

Gnomad4 AFR AF: 0.674

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.0702

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.342

Alfa AF: 0.222 Hom.: 9863

Bravo AF: 0.347

Asia WGS AF: 0.331 AC: 1149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.77

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: rs603424; hg19: chr10-102075479;