10-100291357-G-A

Position:

• chr10-100291357-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_016112.3(PKD2L1):​c.1951C>T​(p.Arg651Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000521 in 1,613,910 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0026 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00030 (1 hom.)
• Consequence: PKD2L1 NM_016112.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.49

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0039155185).
• BP6: Variant 10-100291357-G-A is Benign according to our data. Variant chr10-100291357-G-A is described in ClinVar as [Benign]. Clinvar id is 734157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 400 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKD2L1	NM_016112.3	c.1951C>T	p.Arg651Cys	missense_variant	12/16	ENST00000318222.4	NP_057196.2
PKD2L1	NM_001253837.2	c.1810C>T	p.Arg604Cys	missense_variant	12/16		NP_001240766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKD2L1	ENST00000318222.4	c.1951C>T	p.Arg651Cys	missense_variant	12/16	1	NM_016112.3	ENSP00000325296.3
PKD2L1	ENST00000528248.1	n.*1691C>T		non_coding_transcript_exon_variant	12/16	1		ENSP00000436514.1
PKD2L1	ENST00000528248.1	n.*1691C>T		3_prime_UTR_variant	12/16	1		ENSP00000436514.1
PKD2L1	ENST00000465680.2	c.104-2879C>T		intron_variant		3		ENSP00000434019.1

Frequencies

GnomAD3 genomes AF: 0.00263 AC: 400 AN: 152038 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00897

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000760 AC: 191 AN: 251444 Hom.: 1 AF XY: 0.000633 AC XY: 86 AN XY: 135896

Gnomad AFR exome AF: 0.00941

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.000272

Gnomad SAS exome AF: 0.000621

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000302 AC: 441 AN: 1461754 Hom.: 1 Cov.: 31 AF XY: 0.000274 AC XY: 199 AN XY: 727188

Gnomad4 AFR exome AF: 0.00968

Gnomad4 AMR exome AF: 0.000268

Gnomad4 ASJ exome AF: 0.000191

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.000417

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000117

Gnomad4 OTH exome AF: 0.000745

GnomAD4 genome AF: 0.00263 AC: 400 AN: 152156 Hom.: 2 Cov.: 32 AF XY: 0.00274 AC XY: 204 AN XY: 74374

Gnomad4 AFR AF: 0.00894

Gnomad4 AMR AF: 0.000785

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000546 Hom.: 0

Bravo AF: 0.00298

ESP6500AA AF: 0.0109 AC: 48

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00102 AC: 124

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.30	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.95	L
PrimateAI	Benign	0.18	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.16
Sift	Benign	0.12	T
Sift4G	Benign	0.071	T
Polyphen		0.015	B
Vest4		0.097
MVP		0.29
MPC		0.091
ClinPred		0.012	T
GERP RS		-3.1
Varity_R		0.094
gMVP		0.22

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: rs115252223; hg19: chr10-102051114; COSMIC: COSV58394842; COSMIC: COSV58394842;