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

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 id is 2648706.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KATNAL2	NM_001387690.1 link	c.51+16829C>T		intron_variant	Intron 3 of 17	ENST00000683218.1	NP_001374619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KATNAL2	ENST00000683218.1 link	c.51+16829C>T		intron_variant	Intron 3 of 17		NM_001387690.1	ENSP00000508137.1		Q8IYT4-1

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

Gnomad4 AFR exome

AF:

0.000695

AC:

AN:

8632

Gnomad4 AMR exome

AF:

0.000177

AC:

AN:

22564

Gnomad4 ASJ exome

AF:

0.000269

AC:

AN:

14894

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

29256

Gnomad4 SAS exome

AF:

0.000289

AC:

AN:

55270

Gnomad4 FIN exome

AF:

0.000207

AC:

AN:

29004

Gnomad4 NFE exome

AF:

0.000298

AC:

179

AN:

600994

Gnomad4 Remaining exome

AF:

0.000330

AC:

AN:

33374

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

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Gnomad4 AFR

AF:

0.00

AC:

AN:

Gnomad4 AMR

AF:

0.00

AC:

AN:

Gnomad4 ASJ

AF:

0.000693

AC:

0.000692521

AN:

0.000692521

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000493

AC:

0.000493097

AN:

0.000493097

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000105

AC:

0.000105352

AN:

0.000105352

Gnomad4 OTH

AF:

0.00

AC:

AN:

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

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ELOA3DP: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

DANN

Benign

0.78

Mutation Taster

=100/0

polymorphism

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over