7-32869569-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015483.3(KBTBD2):​c.1648G>T​(p.Val550Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

KBTBD2
NM_015483.3 missense

Scores

2
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91
Variant links:
Genes affected
KBTBD2 (HGNC:21751): (kelch repeat and BTB domain containing 2) Predicted to act upstream of or within with a positive effect on several processes, including glucose metabolic process; phosphatidylinositol 3-kinase signaling; and response to insulin. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2196033).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KBTBD2NM_015483.3 linkc.1648G>T p.Val550Phe missense_variant Exon 4 of 4 ENST00000304056.9 NP_056298.2 Q8IY47A0A024RA38

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KBTBD2ENST00000304056.9 linkc.1648G>T p.Val550Phe missense_variant Exon 4 of 4 1 NM_015483.3 ENSP00000302586.4 Q8IY47

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152126
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
32
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152126
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74300
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1648G>T (p.V550F) alteration is located in exon 4 (coding exon 3) of the KBTBD2 gene. This alteration results from a G to T substitution at nucleotide position 1648, causing the valine (V) at amino acid position 550 to be replaced by a phenylalanine (F). 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
0.25
BayesDel_addAF
Uncertain
0.022
T
BayesDel_noAF
Benign
-0.21
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.057
T
Eigen
Benign
-0.071
Eigen_PC
Benign
0.14
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.97
D
M_CAP
Benign
0.053
D
MetaRNN
Benign
0.22
T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
0.0
N
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-0.29
N
REVEL
Benign
0.24
Sift
Benign
0.049
D
Sift4G
Benign
0.081
T
Polyphen
0.026
B
Vest4
0.39
MutPred
0.43
Loss of catalytic residue at V550 (P = 0.0393);
MVP
0.40
MPC
0.78
ClinPred
0.81
D
GERP RS
4.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2
Varity_R
0.27
gMVP
0.60

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: rs779255249; hg19: chr7-32909181; API