18-47059049-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001387690.1(KATNAL2):​c.451-507C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 151,942 control chromosomes in the GnomAD database, including 13,059 homozygotes. 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: 𝑓 0.41 (13059 hom., 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

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>T		intron	N/A	NP_001374619.1	Q8IYT4-1
	KATNAL2	NM_001353899.1		c.529-507C>T		intron	N/A	NP_001340828.1
	KATNAL2	NM_001353900.1		c.526-507C>T		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>T		intron	N/A	ENSP00000508137.1	Q8IYT4-1
	KATNAL2	ENST00000245121.10	TSL:1	c.235-507C>T		intron	N/A	ENSP00000245121.4	Q8IYT4-2
	KATNAL2	ENST00000591522.2	TSL:1	c.118-507C>T		intron	N/A	ENSP00000467488.2	K7EPQ6

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62760 AN: 151824 Hom.: 13051 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.413 AC: 62796 AN: 151942 Hom.: 13059 Cov.: 32 AF XY: 0.414 AC XY: 30754 AN XY: 74224

African (AFR) AF: 0.362 AC: 15006 AN: 41444

American (AMR) AF: 0.524 AC: 7992 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1619 AN: 3468

East Asian (EAS) AF: 0.496 AC: 2551 AN: 5142

South Asian (SAS) AF: 0.451 AC: 2176 AN: 4820

European-Finnish (FIN) AF: 0.355 AC: 3745 AN: 10548

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28378 AN: 67946

Other (OTH) AF: 0.441 AC: 933 AN: 2114

Alfa AF: 0.420 Hom.: 30605

Bravo AF: 0.424

Asia WGS AF: 0.496 AC: 1722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.62
PhyloP100		-0.86
Mutation Taster		=100/0	polymorphism (auto)

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;