18-47028616-G-T

Variant names:

• chr18-47028616-G-T
• rs756136890
• NM_001387690.1:c.52-17841G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001387690.1(KATNAL2):​c.52-17841G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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: not found (cov: 8)
  • Exomes 𝑓: 0.0000065 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KATNAL2 NM_001387690.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880
• Publications: 0 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]

ELOA3P (HGNC:24617): (elongin A3, pseudogene) The SIII (or elongin) transcription elongation factor complex stimulates the rate of transcription elongation by RNA polymerase II by suppressing the transient pausing of the polymerase at many sites along the DNA template. This gene represents a likely pseudogene of ELOA (GeneID: 6924). [provided by RefSeq, Jun 2020]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06543347).

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.52-17841G>T		intron	N/A	NP_001374619.1	Q8IYT4-1
	KATNAL2	NM_001353899.1		c.130-17841G>T		intron	N/A	NP_001340828.1
	KATNAL2	NM_001353900.1		c.130-17841G>T		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.52-17841G>T		intron	N/A	ENSP00000508137.1	Q8IYT4-1
	KATNAL2	ENST00000245121.10	TSL:1	c.-94-24264G>T		intron	N/A	ENSP00000245121.4	Q8IYT4-2
	KATNAL2	ENST00000591522.2	TSL:1	c.-1-29619G>T		intron	N/A	ENSP00000467488.2	K7EPQ6

Frequencies

GnomAD3 genomes Cov.: 8

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000649 AC: 4 AN: 615866 Hom.: 0 Cov.: 6 AF XY: 0.00000322 AC XY: 1 AN XY: 310152

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

African (AFR) AF: 0.00 AC: 0 AN: 16330

American (AMR) AF: 0.00 AC: 0 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13948

East Asian (EAS) AF: 0.00 AC: 0 AN: 14756

South Asian (SAS) AF: 0.0000988 AC: 4 AN: 40474

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2296

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 463404

Other (OTH) AF: 0.00 AC: 0 AN: 27900

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000197943), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 8

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	2.1
DANN	Benign	0.65
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N
PhyloP100		-0.088
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.091
Sift	Benign	0.22	T
Sift4G	Benign	0.37	T
Polyphen		0.0010	B
Vest4		0.12
MutPred		0.39		Gain of methylation at K405 (P = 0.128)
MVP		0.081
ClinPred		0.12	T
GERP RS		-3.0
Varity_R		0.039
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs756136890; hg19: chr18-44554987;