19-11174531-GG-TA

Variant names:

• chr19-11174531-GG-TA
• NM_001136191.3:c.2009_2010delCCinsTA
• KANK2 p.Ala670Val

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PS1 PP3

The NM_001136191.3(KANK2):​c.2009_2010delCCinsTA​(p.Ala670Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Pathogenic in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KANK2 NM_001136191.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.59
• Publications: 0 publications found

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]

KANK2 Gene-Disease associations (from GenCC):

• wooly hair-palmoplantar keratoderma syndrome

  Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• nephrotic syndrome 16

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PS1: Transcript NM_001136191.3 (KANK2) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136191.3. 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
	KANK2	NM_001136191.3	MANE Select	c.2009_2010delCCinsTA	p.Ala670Val	missense	N/A	NP_001129663.1	Q63ZY3-1
	KANK2	NM_001379548.1		c.2033_2034delCCinsTA	p.Ala678Val	missense	N/A	NP_001366477.1	Q63ZY3-2
	KANK2	NM_001379549.1		c.2033_2034delCCinsTA	p.Ala678Val	missense	N/A	NP_001366478.1	Q63ZY3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KANK2	ENST00000586659.6	TSL:1 MANE Select	c.2009_2010delCCinsTA	p.Ala670Val	missense	N/A	ENSP00000465650.1	Q63ZY3-1
	KANK2	ENST00000589359.5	TSL:5	c.2033_2034delCCinsTA	p.Ala678Val	missense	N/A	ENSP00000468002.1	Q63ZY3-2
	KANK2	ENST00000884142.1		c.2033_2034delCCinsTA	p.Ala678Val	missense	N/A	ENSP00000554201.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-11285207;