Genetic Variant KATNAL2:c.51+16829C>T (chr18-46963752-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001387690.1(KATNAL2):c.51+16829C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000094 ( 0 hom., cov: 1)

Exomes 𝑓: 0.00028 ( 7 hom. )

Failed GnomAD Quality Control

Consequence

KATNAL2
NM_001387690.1 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.45

Publications

0 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 links:

ELOA3DP (HGNC:33511): (elongin A3 family member D, pseudogene) Predicted to be involved in transcription elongation from RNA polymerase II promoter. Predicted to be part of elongin complex. [provided by Alliance of Genome Resources, Apr 2022]

ELOA3DP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 18-46963752-C-T is Benign according to our data. Variant chr18-46963752-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2648706.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KATNAL2	NM_001387690.1	MANE Select	c.51+16829C>T	intron	N/A	NP_001374619.1	Q8IYT4-1
KATNAL2	NM_001353899.1		c.129+16829C>T	intron	N/A	NP_001340828.1
KATNAL2	NM_001353900.1		c.129+16829C>T	intron	N/A	NP_001340829.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KATNAL2	ENST00000683218.1	MANE Select	c.51+16829C>T	intron	N/A	ENSP00000508137.1	Q8IYT4-1
KATNAL2	ENST00000245121.10	TSL:1	c.-95+16829C>T	intron	N/A	ENSP00000245121.4	Q8IYT4-2
KATNAL2	ENST00000591522.2	TSL:1	c.-2+16829C>T	intron	N/A	ENSP00000467488.2	K7EPQ6

Frequencies

GnomAD3 genomes

AF:

0.0000944

AC:

AN:

52986

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000693

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000491

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000105

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000507

AC:

AN:

35524

AF XY:

0.000386

show subpopulations

Gnomad AFR exome

AF:

0.00284

Gnomad AMR exome

AF:

0.000443

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00101

Gnomad NFE exome

AF:

0.000510

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000284

AC:

226

AN:

796198

Hom.:

Cov.:

AF XY:

0.000280

AC XY:

112

AN XY:

399922

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000695

AC:

AN:

8632

American (AMR)

AF:

0.000177

AC:

AN:

22564

Ashkenazi Jewish (ASJ)

AF:

0.000269

AC:

AN:

14894

East Asian (EAS)

AF:

0.00

AC:

AN:

29256

South Asian (SAS)

AF:

0.000289

AC:

AN:

55270

European-Finnish (FIN)

AF:

0.000207

AC:

AN:

29004

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2210

European-Non Finnish (NFE)

AF:

0.000298

AC:

179

AN:

600994

Other (OTH)

AF:

0.000330

AC:

AN:

33374

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.290

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000944

AC:

AN:

52986

Hom.:

Cov.:

AF XY:

0.0000774

AC XY:

AN XY:

25844

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

7414

American (AMR)

AF:

0.00

AC:

AN:

5096

Ashkenazi Jewish (ASJ)

AF:

0.000693

AC:

AN:

1444

East Asian (EAS)

AF:

0.00

AC:

AN:

2850

South Asian (SAS)

AF:

0.000493

AC:

AN:

2028

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4696

Middle Eastern (MID)

AF:

0.00

AC:

AN:

100

European-Non Finnish (NFE)

AF:

0.000105

AC:

AN:

28476

Other (OTH)

AF:

0.00

AC:

AN:

716

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.285

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

(source)

DANN

Benign

0.78

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over