rs2576036

Variant names:

• chr18-47060731-A-C
• rs2576036
• NM_001387690.1:c.549+1077A>C

Variant summary

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

The NM_001387690.1(KATNAL2):​c.549+1077A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 151,960 control chromosomes in the GnomAD database, including 14,769 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 0.44 (14769 hom., cov: 31)
• Consequence: KATNAL2 NM_001387690.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.627
• Publications: 6 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.534 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.549+1077A>C		intron	N/A	NP_001374619.1
	KATNAL2	NM_001353899.1		c.627+1077A>C		intron	N/A	NP_001340828.1
	KATNAL2	NM_001353900.1		c.624+1077A>C		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.549+1077A>C		intron	N/A	ENSP00000508137.1
	KATNAL2	ENST00000245121.10	TSL:1	c.333+1077A>C		intron	N/A	ENSP00000245121.4
	KATNAL2	ENST00000591522.2	TSL:1	c.216+1077A>C		intron	N/A	ENSP00000467488.2

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66723 AN: 151842 Hom.: 14763 Cov.: 31

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.439 AC: 66756 AN: 151960 Hom.: 14769 Cov.: 31 AF XY: 0.440 AC XY: 32644 AN XY: 74266

African (AFR) AF: 0.369 AC: 15286 AN: 41464

American (AMR) AF: 0.543 AC: 8298 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1667 AN: 3470

East Asian (EAS) AF: 0.505 AC: 2603 AN: 5154

South Asian (SAS) AF: 0.456 AC: 2193 AN: 4806

European-Finnish (FIN) AF: 0.394 AC: 4166 AN: 10562

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31139 AN: 67928

Other (OTH) AF: 0.473 AC: 995 AN: 2102

Alfa AF: 0.458 Hom.: 21538

Bravo AF: 0.447

Asia WGS AF: 0.507 AC: 1761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.2
DANN	Benign	0.72
PhyloP100		-0.63
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: rs2576036; hg19: chr18-44587102;