chr5-137940136-A-C

Variant names:

• chr5-137940136-A-C
• rs376480186
• ENST00000290431.5:c.1831A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014386.4(PKD2L2):​c.1831A>C​(p.Lys611Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,613,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: PKD2L2 NM_014386.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.67
• Publications: 1 publications found

Genes affected

PKD2L2 (HGNC:9012): (polycystin 2 like 2, transient receptor potential cation channel) Predicted to enable calcium channel activity. Predicted to be involved in detection of mechanical stimulus. Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

FAM13B (HGNC:1335): (family with sequence similarity 13 member B) Predicted to enable GTPase activator activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17755201).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014386.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM13B	NM_001385994.1	MANE Select	c.*89T>G		3_prime_UTR	Exon 24 of 24	NP_001372923.1	A0A8I5KSB9
	PKD2L2	NM_001300921.2	MANE Select	c.*18-2248A>C		intron	N/A	NP_001287850.1	Q9NZM6-1
	PKD2L2	NM_014386.4		c.1831A>C	p.Lys611Gln	missense	Exon 14 of 14	NP_055201.2	Q9NZM6-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD2L2	ENST00000290431.5	TSL:1	c.1831A>C	p.Lys611Gln	missense	Exon 14 of 14	ENSP00000290431.5	Q9NZM6-5
	FAM13B	ENST00000689681.1	MANE Select	c.*89T>G		3_prime_UTR	Exon 24 of 24	ENSP00000509788.1	A0A8I5KSB9
	FAM13B	ENST00000033079.7	TSL:1	c.*89T>G		3_prime_UTR	Exon 23 of 23	ENSP00000033079.3	Q9NYF5-1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152244 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000201 AC: 5 AN: 248856 AF XY: 0.0000222

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000358

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1461728 Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11 AN XY: 727158

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1111900

Other (OTH) AF: 0.0000166 AC: 1 AN: 60386

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152244 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74372

African (AFR) AF: 0.00 AC: 0 AN: 41462

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000189

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	13
DANN	Uncertain	0.99
Eigen	Benign	0.00048
Eigen_PC	Benign	0.078
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.25	T
M_CAP	Uncertain	0.090	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.78	T
PhyloP100		2.7
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.066
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.13	T
Polyphen		0.40	B
Vest4		0.24
MVP		0.76
MPC		0.77
ClinPred		0.67	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs376480186; hg19: chr5-137275825;