dbSNP rs151143404: ELOA2:p.Val735Leu (chr18-47033062-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016427.3(ELOA2):c.2203G>T(p.Val735Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

ELOA2
NM_016427.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.875

Publications

0 publications found

Variant links:

Genes affected

ELOA2 (HGNC:30771): (elongin A2) This gene encodes the transcriptionally active subunit of the SIII (or elongin) transcription elongation factor complex, which also includes two regulatory subunits, elongins B and C. This complex acts to increase the rate of RNA chain elongation by RNA polymerase II by suppressing transient pausing of the polymerase at many sites along the DNA template. Whereas a related protein with similar function, elongin A, is ubiquitously expressed, the encoded protein is specifically expressed in the testis, suggesting it may have a role in spermatogenesis. [provided by RefSeq, Jul 2008]

ELOA2 links:

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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0593338).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016427.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ELOA2	NM_016427.3	MANE Select	c.2203G>T	p.Val735Leu	missense	Exon 1 of 1	NP_057511.2
KATNAL2	NM_001387690.1	MANE Select	c.52-13395C>A		intron	N/A	NP_001374619.1	Q8IYT4-1
KATNAL2	NM_001353899.1		c.130-13395C>A		intron	N/A	NP_001340828.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ELOA2	ENST00000332567.6	TSL:6 MANE Select	c.2203G>T	p.Val735Leu	missense	Exon 1 of 1	ENSP00000331302.4	Q8IYF1
KATNAL2	ENST00000683218.1	MANE Select	c.52-13395C>A		intron	N/A	ENSP00000508137.1	Q8IYT4-1
KATNAL2	ENST00000245121.10	TSL:1	c.-94-19818C>A		intron	N/A	ENSP00000245121.4	Q8IYT4-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

4.6

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.12

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.51

M_CAP

Benign

0.0034

MetaRNN

Benign

0.059

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

-0.88

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.89

REVEL

Benign

0.13

Sift

Benign

0.060

Sift4G

Uncertain

0.048

Polyphen

0.63

Vest4

0.041

MutPred

0.30

Loss of catalytic residue at V735 (P = 0.0121)

MVP

0.040

MPC

0.044

ClinPred

0.18

GERP RS

-3.2

Varity_R

0.046

gMVP

0.13

Mutation Taster

=99/1

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over