NM_001387690.1:c.451-507C>G

Variant names:

• chr18-47059049-C-G
• rs2576037
• NM_001387690.1:c.451-507C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001387690.1(KATNAL2):​c.451-507C>G variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KATNAL2 NM_001387690.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.856
• Publications: 24 publications found

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]

KATNAL2 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387690.1. 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
	KATNAL2	NM_001387690.1	MANE Select	c.451-507C>G		intron	N/A	NP_001374619.1	Q8IYT4-1
	KATNAL2	NM_001353899.1		c.529-507C>G		intron	N/A	NP_001340828.1
	KATNAL2	NM_001353900.1		c.526-507C>G		intron	N/A	NP_001340829.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KATNAL2	ENST00000683218.1	MANE Select	c.451-507C>G		intron	N/A	ENSP00000508137.1	Q8IYT4-1
	KATNAL2	ENST00000245121.10	TSL:1	c.235-507C>G		intron	N/A	ENSP00000245121.4	Q8IYT4-2
	KATNAL2	ENST00000591522.2	TSL:1	c.118-507C>G		intron	N/A	ENSP00000467488.2	K7EPQ6

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.38
DANN	Benign	0.38
PhyloP100		-0.86

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: rs2576037; hg19: chr18-44585420;