18-46946253-T-A

Variant names:

• chr18-46946253-T-A
• NM_001387690.1:c.-313T>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001353899.1(KATNAL2):​c.37T>A​(p.Phe13Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KATNAL2 NM_001353899.1 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.288

Genes affected

KATNAL2 (HGNC:25387): (katanin catalytic subunit A1 like 2) Predicted to enable microtubule-severing ATPase activity. Predicted to be involved in cytoplasmic microtubule organization. Located in cytoplasm; microtubule; and spindle pole. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KATNAL2	NM_001387690.1	c.-313T>A		5_prime_UTR_variant	Exon 2 of 18	ENST00000683218.1	NP_001374619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KATNAL2	ENST00000683218	c.-313T>A		5_prime_UTR_variant	Exon 2 of 18		NM_001387690.1	ENSP00000508137.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

KATNAL2-related disorder Uncertain:1

Mar 21, 2024

PreventionGenetics, part of Exact Sciences

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

The KATNAL2 c.37T>A variant is predicted to result in the amino acid substitution p.Phe13Ile. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.66

Splicing

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: chr18-44526216;