ENST00000290431.5:c.1831A>G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000290431.5(PKD2L2):​c.1831A>G​(p.Lys611Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K611Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PKD2L2 ENST00000290431.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.67

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.118980676).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM13B	NM_001385994.1	c.*89T>C		3_prime_UTR_variant	Exon 24 of 24	ENST00000689681.1	NP_001372923.1
PKD2L2	NM_001300921.2	c.*18-2248A>G		intron_variant	Intron 14 of 14	ENST00000508883.6	NP_001287850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM13B	ENST00000689681	c.*89T>C		3_prime_UTR_variant	Exon 24 of 24		NM_001385994.1	ENSP00000509788.1
PKD2L2	ENST00000508883.6	c.*18-2248A>G		intron_variant	Intron 14 of 14	1	NM_001300921.2	ENSP00000424725.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461728 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727158

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	13
DANN	Uncertain	1.0
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.067
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.081	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.91	T
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.049
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.10	T
Polyphen		0.0010	B
Vest4		0.13
MutPred		0.26		Loss of MoRF binding (P = 5e-04);
MVP		0.67
MPC		0.87
ClinPred		0.65	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-137275825;