rs1555820663

chr19-11193539-T-C

Variant summary

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

The NM_001136191.3(KANK2):c.541A>G(p.Ser181Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000056 in 1,606,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S181N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: KANK2 NM_001136191.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter P:1
• Conservation: PhyloP100: 3.42

Genes affected

KANK2 (HGNC:29300): (KN motif and ankyrin repeat domains 2) This gene encodes a member of the KN motif and ankyrin repeat domains (KANK) family of proteins, which play a role in cytoskeletal formation by regulating actin polymerization. The encoded protein functions in the sequestration of steroid receptor coactivators and possibly other proteins. Mutations in this gene are associated with impaired kidney podocyte function and nephrotic syndrome, and keratoderma and woolly hair. [provided by RefSeq, Jul 2016]

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=0.14831248).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KANK2	NM_001136191.3	c.541A>G	p.Ser181Gly	missense_variant	4/13	ENST00000586659.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KANK2	ENST00000586659.6	c.541A>G	p.Ser181Gly	missense_variant	4/13	1	NM_001136191.3	P1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152112 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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000550 AC: 8 AN: 1453984 Hom.: 0 Cov.: 37 AF XY: 0.00000138 AC XY: 1 AN XY: 723542

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152112 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74314

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000336 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Nephrotic syndrome 16 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
Cadd	Benign	21
Dann	Benign	0.65
DEOGEN2	Benign	0.095	T;.;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.34	N
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.93	L;L;L
MutationTaster	Benign	0.97	N;N;N;N;N
PrimateAI	Uncertain	0.73	T
Sift4G	Benign	0.18	T;T;T
Polyphen		0.043	B;D;P
Vest4		0.34
MutPred		0.27		Loss of glycosylation at S181 (P = 0.0068);Loss of glycosylation at S181 (P = 0.0068);Loss of glycosylation at S181 (P = 0.0068);
MVP		0.18
ClinPred		0.67	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.24
gMVP		0.53

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: rs1555820663; hg19: chr19-11304215;