rs7233515

chr18-47059584-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001387690.1(KATNAL2):c.479G>A(p.Ser160Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 1,608,632 control chromosomes in the GnomAD database, including 134,973 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.40 (12195 hom., cov: 33)
  • Exomes 𝑓: 0.41 (122778 hom.)
• Consequence: KATNAL2 NM_001387690.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.903

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.368946E-5).
• BP6: Variant 18-47059584-G-A is Benign according to our data. Variant chr18-47059584-G-A is described in ClinVar as [Benign]. Clinvar id is 587805.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KATNAL2	NM_001387690.1	c.479G>A	p.Ser160Asn	missense_variant	8/18	ENST00000683218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KATNAL2	ENST00000683218.1	c.479G>A	p.Ser160Asn	missense_variant	8/18		NM_001387690.1	P1

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60759 AN: 151896 Hom.: 12190 Cov.: 33

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.424

GnomAD3 exomes AF: 0.430 AC: 108118 AN: 251168 Hom.: 23861 AF XY: 0.428 AC XY: 58094 AN XY: 135756

Gnomad AFR exome AF: 0.354

Gnomad AMR exome AF: 0.558

Gnomad ASJ exome AF: 0.448

Gnomad EAS exome AF: 0.490

Gnomad SAS exome AF: 0.460

Gnomad FIN exome AF: 0.360

Gnomad NFE exome AF: 0.398

Gnomad OTH exome AF: 0.410

GnomAD4 exome AF: 0.408 AC: 593871 AN: 1456620 Hom.: 122778 Cov.: 32 AF XY: 0.408 AC XY: 295938 AN XY: 724938

Gnomad4 AFR exome AF: 0.339

Gnomad4 AMR exome AF: 0.550

Gnomad4 ASJ exome AF: 0.451

Gnomad4 EAS exome AF: 0.503

Gnomad4 SAS exome AF: 0.455

Gnomad4 FIN exome AF: 0.363

Gnomad4 NFE exome AF: 0.398

Gnomad4 OTH exome AF: 0.415

GnomAD4 genome AF: 0.400 AC: 60790 AN: 152012 Hom.: 12195 Cov.: 33 AF XY: 0.402 AC XY: 29890 AN XY: 74302

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.510

Gnomad4 ASJ AF: 0.446

Gnomad4 EAS AF: 0.489

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.427

Alfa AF: 0.405 Hom.: 27332

Bravo AF: 0.409

TwinsUK AF: 0.405 AC: 1503

ALSPAC AF: 0.407 AC: 1569

ESP6500AA AF: 0.347 AC: 1529

ESP6500EA AF: 0.400 AC: 3438

ExAC AF: 0.423 AC: 51409

Asia WGS AF: 0.489 AC: 1696 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 22, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.43
Cadd	Benign	0.31
Dann	Benign	0.84
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.50	T;T;T
MetaRNN	Benign	0.000064	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.34	T
Sift4G	Benign	0.11	T;T;T
Polyphen		0.0010	.;.;B
Vest4		0.093, 0.037
MPC		0.10
ClinPred		0.016	T
GERP RS		-4.8
Varity_R		0.041
gMVP		0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs7233515; hg19: chr18-44585955; COSMIC: COSV55293067; COSMIC: COSV55293067;