Variant 11-34159316-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_145804.3(ABTB2):c.2677A>C(p.Met893Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,461,686 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: 0.000033 ( 0 hom. )

Consequence

ABTB2
NM_145804.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.41

Variant links:

Genes affected

ABTB2 (HGNC:23842): (ankyrin repeat and BTB domain containing 2) Predicted to enable protein heterodimerization activity. Predicted to act upstream of or within cellular response to toxic substance. [provided by Alliance of Genome Resources, Apr 2022]

ABTB2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28132546).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABTB2	NM_145804.3 linkuse as main transcript	c.2677A>C	p.Met893Leu	missense_variant	14/17	ENST00000435224.3	NP_665803.2	Q8N961-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABTB2	ENST00000435224.3 linkuse as main transcript	c.2677A>C	p.Met893Leu	missense_variant	14/17	1	NM_145804.3	ENSP00000410157.2		Q8N961-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251376

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000328

AC:

AN:

1461686

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

727172

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:

0.0000432

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

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

Oct 19, 2024

The c.2677A>C (p.M893L) alteration is located in exon 14 (coding exon 14) of the ABTB2 gene. This alteration results from a A to C substitution at nucleotide position 2677, causing the methionine (M) at amino acid position 893 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

Benign

0.29

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.10

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.026

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.2

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.040

REVEL

Benign

0.093

Sift

Uncertain

0.013

Sift4G

Benign

0.085

Vest4

0.46

MVP

0.50

MPC

0.15

ClinPred

0.59

GERP RS

4.2

Varity_R

0.21

gMVP

0.31

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