chr19-1986871-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017797.4(BTBD2):​c.1375G>A​(p.Val459Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,312 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

BTBD2
NM_017797.4 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.73
Variant links:
Genes affected
BTBD2 (HGNC:15504): (BTB domain containing 2) The C-terminus of the protein encoded by this gene binds topoisomerase I. The N-terminus contains a proline-rich region and a BTB/POZ domain (broad-complex, Tramtrack and bric a brac/Pox virus and Zinc finger), both of which are typically involved in protein-protein interactions. Subcellularly, the protein localizes to cytoplasmic bodies. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BTBD2NM_017797.4 linkc.1375G>A p.Val459Met missense_variant Exon 8 of 9 ENST00000255608.9 NP_060267.2 Q9BX70-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BTBD2ENST00000255608.9 linkc.1375G>A p.Val459Met missense_variant Exon 8 of 9 1 NM_017797.4 ENSP00000255608.3 Q9BX70-1
BTBD2ENST00000589685.2 linkn.1169G>A non_coding_transcript_exon_variant Exon 5 of 6 1
BTBD2ENST00000592895.5 linkn.1510G>A non_coding_transcript_exon_variant Exon 2 of 3 2
BTBD2ENST00000592082.5 linkc.*93G>A downstream_gene_variant 5 ENSP00000481163.1 A0A087WXN3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460312
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
726438
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:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 16, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1375G>A (p.V459M) alteration is located in exon 8 (coding exon 8) of the BTBD2 gene. This alteration results from a G to A substitution at nucleotide position 1375, causing the valine (V) at amino acid position 459 to be replaced by a methionine (M). 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
Pathogenic
0.57
BayesDel_addAF
Benign
-0.099
T
BayesDel_noAF
Benign
-0.38
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.096
T
Eigen
Benign
0.062
Eigen_PC
Benign
-0.044
FATHMM_MKL
Benign
0.52
D
LIST_S2
Benign
0.81
T
M_CAP
Uncertain
0.23
D
MetaRNN
Uncertain
0.54
D
MetaSVM
Uncertain
-0.24
T
MutationAssessor
Benign
1.7
L
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-2.1
N
REVEL
Uncertain
0.34
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0030
D
Polyphen
0.92
P
Vest4
0.38
MutPred
0.80
Loss of ubiquitination at K454 (P = 0.0801);
MVP
0.42
MPC
1.1
ClinPred
0.88
D
GERP RS
0.16
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.57
gMVP
0.25

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

hg19: chr19-1986870; API