19-48796502-T-C

Variant summary

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

The NM_001190.4(BCAT2):​c.1066A>G​(p.Asn356Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

BCAT2
NM_001190.4 missense, splice_region

Scores

19
Splicing: ADA: 0.00002065
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.615
Variant links:
Genes affected
BCAT2 (HGNC:977): (branched chain amino acid transaminase 2) This gene encodes a branched chain aminotransferase found in mitochondria. The encoded protein forms a dimer that catalyzes the first step in the production of the branched chain amino acids leucine, isoleucine, and valine. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

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=0.05326432).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BCAT2NM_001190.4 linkc.1066A>G p.Asn356Asp missense_variant, splice_region_variant Exon 10 of 11 ENST00000316273.11 NP_001181.2 O15382-1
BCAT2NM_001284325.2 linkc.946A>G p.Asn316Asp missense_variant, splice_region_variant Exon 11 of 12 NP_001271254.1 O15382B3KSI3
BCAT2NM_001164773.2 linkc.790A>G p.Asn264Asp missense_variant, splice_region_variant Exon 8 of 9 NP_001158245.1 O15382-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BCAT2ENST00000316273.11 linkc.1066A>G p.Asn356Asp missense_variant, splice_region_variant Exon 10 of 11 1 NM_001190.4 ENSP00000322991.5 O15382-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152210
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
33
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152210
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Sep 06, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 356 of the BCAT2 protein (p.Asn356Asp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BCAT2-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.070
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.83
CADD
Benign
0.97
DANN
Benign
0.63
DEOGEN2
Benign
0.22
.;T;T;T;T;T;T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.10
N
LIST_S2
Benign
0.091
T;.;T;T;T;T;T
M_CAP
Benign
0.0027
T
MetaRNN
Benign
0.053
T;T;T;T;T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
-0.48
.;.;N;.;.;.;.
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.58
N;N;N;.;.;.;.
REVEL
Benign
0.034
Sift
Benign
1.0
T;T;T;.;.;.;.
Sift4G
Benign
0.71
T;T;T;T;T;T;T
Polyphen
0.0
B;B;B;.;B;.;.
Vest4
0.086
MutPred
0.45
.;.;Loss of methylation at K353 (P = 0.0756);.;.;.;Loss of methylation at K353 (P = 0.0756);
MVP
0.12
MPC
0.45
ClinPred
0.043
T
GERP RS
-6.1
Varity_R
0.25
gMVP
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000021
dbscSNV1_RF
Benign
0.0
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.

Other links and lift over

dbSNP: rs2034522370; hg19: chr19-49299759; API