rs7233515

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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. 15/21 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.903

Publications

35 publications found

Variant links:

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

KATNAL2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 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 VariationId is 587805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
KATNAL2	NM_001387690.1 link	c.479G>A	p.Ser160Asn	missense_variant	Exon 8 of 18	ENST00000683218.1	NP_001374619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KATNAL2	ENST00000683218.1 link	c.479G>A	p.Ser160Asn	missense_variant	Exon 8 of 18		NM_001387690.1	ENSP00000508137.1

Frequencies

GnomAD3 genomes

AF:

0.400

AC:

60759

AN:

151896

Hom.:

12190

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.430

AC:

108118

AN:

251168

AF XY:

0.428

show subpopulations

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 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.:

AF XY:

0.408

AC XY:

295938

AN XY:

724938

show subpopulations

African (AFR)

AF:

0.339

AC:

11333

AN:

33382

American (AMR)

AF:

0.550

AC:

24594

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.451

AC:

11773

AN:

26102

East Asian (EAS)

AF:

0.503

AC:

19965

AN:

39656

South Asian (SAS)

AF:

0.455

AC:

39155

AN:

86120

European-Finnish (FIN)

AF:

0.363

AC:

19357

AN:

53376

Middle Eastern (MID)

AF:

0.389

AC:

2237

AN:

5758

European-Non Finnish (NFE)

AF:

0.398

AC:

440502

AN:

1107380

Other (OTH)

AF:

0.415

AC:

24955

AN:

60156

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

16275

32550

48825

65100

81375

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13814

27628

41442

55256

69070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.400

AC:

60790

AN:

152012

Hom.:

12195

Cov.:

AF XY:

0.402

AC XY:

29890

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.353

AC:

14650

AN:

41460

American (AMR)

AF:

0.510

AC:

7787

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.446

AC:

1549

AN:

3470

East Asian (EAS)

AF:

0.489

AC:

2522

AN:

5160

South Asian (SAS)

AF:

0.447

AC:

2151

AN:

4812

European-Finnish (FIN)

AF:

0.350

AC:

3693

AN:

10554

Middle Eastern (MID)

AF:

0.353

AC:

103

AN:

292

European-Non Finnish (NFE)

AF:

0.399

AC:

27142

AN:

67968

Other (OTH)

AF:

0.427

AC:

902

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1876

3752

5628

7504

9380

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

586

1172

1758

2344

2930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.404

Hom.:

44978

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 22, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Benign

0.31

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.027

.;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.50

T;T;T

MetaRNN

Benign

0.000064

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

.;.;L

PhyloP100

-0.90

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.51

.;N;N

REVEL

Benign

0.12

Sift

Benign

0.22

.;T;T

Sift4G

Benign

0.11

T;T;T

Polyphen

0.0010

.;.;B

Vest4

0.093, 0.037

MPC

0.10

ClinPred

0.016

GERP RS

-4.8

Varity_R

0.041

gMVP

0.46

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over