19-1987584-C-G

Variant summary

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

The NM_017797.4(BTBD2):​c.1097G>C​(p.Cys366Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,612,530 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

BTBD2
NM_017797.4 missense

Scores

4
8
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.62
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.1097G>C p.Cys366Ser missense_variant Exon 6 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.1097G>C p.Cys366Ser missense_variant Exon 6 of 9 1 NM_017797.4 ENSP00000255608.3 Q9BX70-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152084
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000483
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
GnomAD3 exomes
AF:
0.00000404
AC:
1
AN:
247794
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134518
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:
0.00000895
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460446
Hom.:
0
Cov.:
36
AF XY:
0.00
AC XY:
0
AN XY:
726474
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
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:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152084
Hom.:
0
Cov.:
31
AF XY:
0.0000269
AC XY:
2
AN XY:
74290
show subpopulations
Gnomad4 AFR
AF:
0.0000483
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
Bravo
AF:
0.00000378
ExAC
AF:
0.00000825
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 08, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1097G>C (p.C366S) alteration is located in exon 6 (coding exon 6) of the BTBD2 gene. This alteration results from a G to C substitution at nucleotide position 1097, causing the cysteine (C) at amino acid position 366 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
Uncertain
0.56
BayesDel_addAF
Pathogenic
0.32
D
BayesDel_noAF
Pathogenic
0.22
CADD
Uncertain
25
DANN
Uncertain
0.98
DEOGEN2
Benign
0.22
T;T
Eigen
Uncertain
0.33
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.95
D;D
M_CAP
Benign
0.062
D
MetaRNN
Uncertain
0.67
D;D
MetaSVM
Benign
-0.44
T
MutationAssessor
Benign
1.9
L;.
PrimateAI
Pathogenic
0.86
D
PROVEAN
Pathogenic
-6.2
D;.
REVEL
Uncertain
0.61
Sift
Benign
0.31
T;.
Sift4G
Benign
0.23
T;.
Polyphen
0.90
P;.
Vest4
0.92
MutPred
0.49
Gain of disorder (P = 0.0152);.;
MVP
0.88
MPC
0.84
ClinPred
0.66
D
GERP RS
3.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.7
Varity_R
0.66
gMVP
0.74

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: rs745309425; hg19: chr19-1987583; API