10-100291335-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_016112.3(PKD2L1):c.1973A>T(p.Gln658Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00167 in 1,614,076 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0080 (21 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (13 hom.)
• Consequence: PKD2L1 NM_016112.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.93

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0048840344).
• BP6: Variant 10-100291335-T-A is Benign according to our data. Variant chr10-100291335-T-A is described in ClinVar as [Benign]. Clinvar id is 779120.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00803 (1223/152274) while in subpopulation AFR AF= 0.0267 (1111/41540). AF 95% confidence interval is 0.0254. There are 21 homozygotes in gnomad4. There are 601 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1220 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKD2L1	NM_016112.3	c.1973A>T	p.Gln658Leu	missense_variant	12/16	ENST00000318222.4
PKD2L1	NM_001253837.2	c.1832A>T	p.Gln611Leu	missense_variant	12/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKD2L1	ENST00000318222.4	c.1973A>T	p.Gln658Leu	missense_variant	12/16	1	NM_016112.3	P1
PKD2L1	ENST00000528248.1	c.*1713A>T		3_prime_UTR_variant, NMD_transcript_variant	12/16	1
PKD2L1	ENST00000465680.2	c.105-2857A>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.00802 AC: 1220 AN: 152156 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.0267

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00484

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00908

GnomAD3 exomes AF: 0.00232 AC: 584 AN: 251438 Hom.: 7 AF XY: 0.00183 AC XY: 249 AN XY: 135898

Gnomad AFR exome AF: 0.0278

Gnomad AMR exome AF: 0.00223

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000392

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000273

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00101 AC: 1480 AN: 1461802 Hom.: 13 Cov.: 31 AF XY: 0.000846 AC XY: 615 AN XY: 727210

Gnomad4 AFR exome AF: 0.0290

Gnomad4 AMR exome AF: 0.00237

Gnomad4 ASJ exome AF: 0.000306

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000301

Gnomad4 FIN exome AF: 0.0000936

Gnomad4 NFE exome AF: 0.000206

Gnomad4 OTH exome AF: 0.00205

GnomAD4 genome AF: 0.00803 AC: 1223 AN: 152274 Hom.: 21 Cov.: 32 AF XY: 0.00807 AC XY: 601 AN XY: 74460

Gnomad4 AFR AF: 0.0267

Gnomad4 AMR AF: 0.00477

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.00155 Hom.: 4

Bravo AF: 0.00957

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0295 AC: 130

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00292 AC: 355

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000296

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

Jun 05, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.16
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.0049	T
MetaSVM	Benign	-0.29	T
MutationAssessor	Uncertain	2.6	M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.39
Sift	Benign	0.15	T
Sift4G	Benign	0.34	T
Polyphen		0.19	B
Vest4		0.54
MVP		0.80
MPC		0.20
ClinPred		0.028	T
GERP RS		5.8
Varity_R		0.41
gMVP		0.60

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: rs114804435; hg19: chr10-102051092;