chr18-47033062-C-G

Position:

chr18-47033062-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016427.3(ELOA2):c.2203G>C(p.Val735Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

ELOA2
NM_016427.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.875

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04153794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELOA2	NM_016427.3 linkuse as main transcript	c.2203G>C	p.Val735Leu	missense_variant	1/1	ENST00000332567.6	NP_057511.2
KATNAL2	NM_001387690.1 linkuse as main transcript	c.52-13395C>G		intron_variant		ENST00000683218.1	NP_001374619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELOA2	ENST00000332567.6 linkuse as main transcript	c.2203G>C	p.Val735Leu	missense_variant	1/1		NM_016427.3	ENSP00000331302	P1
KATNAL2	ENST00000683218.1 linkuse as main transcript	c.52-13395C>G		intron_variant			NM_001387690.1	ENSP00000508137	P1	Q8IYT4-1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000120

AC:

AN:

250566

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000150

Gnomad OTH exome

AF:

0.000492

GnomAD4 exome

AF:

0.000140

AC:

204

AN:

1461790

Hom.:

Cov.:

AF XY:

0.000133

AC XY:

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000151

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000105

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000203

Hom.:

Bravo

AF:

0.000136

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000132

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2023

The c.2203G>C (p.V735L) alteration is located in exon 1 (coding exon 1) of the TCEB3B gene. This alteration results from a G to C substitution at nucleotide position 2203, causing the valine (V) at amino acid position 735 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.74

CADD

Benign

4.9

DANN

Benign

0.90

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.51

T;T

M_CAP

Benign

0.0035

MetaRNN

Benign

0.042

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.89

N;.

REVEL

Benign

0.13

Sift

Benign

0.060

T;.

Sift4G

Uncertain

0.048

D;T

Polyphen

0.63

P;.

Vest4

0.041

MutPred

0.30

Loss of catalytic residue at V735 (P = 0.0121);.;

MVP

0.040

MPC

0.044

ClinPred

0.044

GERP RS

-3.2

Varity_R

0.046

gMVP

0.13

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