Genetic Variant NM_016427.3:c.2027C>A (chr18-47033238-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_016427.3(ELOA2):c.2027C>A(p.Ser676Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ELOA2
NM_016427.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.849

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:

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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=0.060863227).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELOA2	NM_016427.3 link	c.2027C>A	p.Ser676Tyr	missense_variant	Exon 1 of 1	ENST00000332567.6	NP_057511.2	Q8IYF1
KATNAL2	NM_001387690.1 link	c.52-13219G>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
ELOA2	ENST00000332567.6 link	c.2027C>A	p.Ser676Tyr	missense_variant	Exon 1 of 1	6	NM_016427.3	ENSP00000331302.4		Q8IYF1
KATNAL2	ENST00000683218.1 link	c.52-13219G>T		intron_variant	Intron 3 of 17		NM_001387690.1	ENSP00000508137.1		Q8IYT4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461520

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727058

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.12

DANN

Benign

0.78

DEOGEN2

Benign

0.0059

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.64

T;T

M_CAP

Benign

0.0012

MetaRNN

Benign

0.061

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

N;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.11

N;.

REVEL

Benign

0.041

Sift

Benign

0.44

T;.

Sift4G

Benign

0.17

T;T

Polyphen

0.0

B;.

Vest4

0.16

MutPred

0.17

Loss of glycosylation at S676 (P = 0.0297);.;

MVP

0.040

MPC

0.049

ClinPred

0.15

GERP RS

-0.63

Varity_R

0.026

gMVP

0.15

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over