10-100290141-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_016112.3(PKD2L1):c.2127-3C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000547 in 1,614,060 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0029 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00030 (2 hom.)
• Consequence: PKD2L1 NM_016112.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0007053
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.34

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 10-100290141-G-A is Benign according to our data. Variant chr10-100290141-G-A is described in ClinVar as [Benign]. Clinvar id is 716402.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 440 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKD2L1	NM_016112.3	c.2127-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000318222.4
PKD2L1	NM_001253837.2	c.1986-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKD2L1	ENST00000318222.4	c.2127-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_016112.3	P1
PKD2L1	ENST00000528248.1	c.*1867-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		1
PKD2L1	ENST00000465680.2	c.105-1663C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.00289 AC: 440 AN: 152182 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000788 AC: 198 AN: 251146 Hom.: 1 AF XY: 0.000567 AC XY: 77 AN XY: 135712

Gnomad AFR exome AF: 0.0112

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000303 AC: 443 AN: 1461760 Hom.: 2 Cov.: 32 AF XY: 0.000270 AC XY: 196 AN XY: 727190

Gnomad4 AFR exome AF: 0.0112

Gnomad4 AMR exome AF: 0.000358

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.000679

GnomAD4 genome AF: 0.00289 AC: 440 AN: 152300 Hom.: 4 Cov.: 32 AF XY: 0.00269 AC XY: 200 AN XY: 74476

Gnomad4 AFR AF: 0.0103

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.00134 Hom.: 0

Bravo AF: 0.00357

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 16, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	11
Dann	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00071
dbscSNV1_RF	Benign	0.19
SpliceAI score (max)		0.030		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: rs142195598; hg19: chr10-102049898;