19-1986946-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_017797.4(BTBD2):​c.1300G>A​(p.Gly434Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

BTBD2
NM_017797.4 missense

Scores

3
11
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.75
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.889

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BTBD2NM_017797.4 linkc.1300G>A p.Gly434Ser 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.1300G>A p.Gly434Ser missense_variant Exon 8 of 9 1 NM_017797.4 ENSP00000255608.3 Q9BX70-1
BTBD2ENST00000589685.2 linkn.1094G>A non_coding_transcript_exon_variant Exon 5 of 6 1
BTBD2ENST00000592895.5 linkn.1435G>A non_coding_transcript_exon_variant Exon 2 of 3 2
BTBD2ENST00000592082.5 linkc.*18G>A downstream_gene_variant 5 ENSP00000481163.1 A0A087WXN3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000400
AC:
1
AN:
250288
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135294
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:
0.00000883
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1460868
Hom.:
0
Cov.:
34
AF XY:
0.00000275
AC XY:
2
AN XY:
726696
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378
EpiCase
AF:
0.00
EpiControl
AF:
0.0000594

ClinVar

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

Submissions by phenotype

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

The c.1300G>A (p.G434S) 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 1300, causing the glycine (G) at amino acid position 434 to be replaced by a serine (S). 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
0.82
BayesDel_addAF
Uncertain
0.079
D
BayesDel_noAF
Benign
-0.12
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.078
T
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.95
D
M_CAP
Uncertain
0.19
D
MetaRNN
Pathogenic
0.89
D
MetaSVM
Uncertain
-0.12
T
MutationAssessor
Benign
1.8
L
PrimateAI
Pathogenic
0.92
D
PROVEAN
Uncertain
-2.8
D
REVEL
Uncertain
0.55
Sift
Benign
0.074
T
Sift4G
Uncertain
0.043
D
Polyphen
1.0
D
Vest4
0.89
MutPred
0.62
Loss of sheet (P = 0.0126);
MVP
0.63
MPC
1.4
ClinPred
0.95
D
GERP RS
4.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.63
gMVP
0.41

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.

Other links and lift over

dbSNP: rs1448599067; hg19: chr19-1986945; API