chr2-241559515-C-T

Variant summary

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

The NM_032515.5(BOK):​c.32C>T​(p.Ala11Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000419 in 1,502,550 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000042 ( 1 hom. )

Consequence

BOK
NM_032515.5 missense

Scores

5
6
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.63
Variant links:
Genes affected
BOK (HGNC:1087): (BCL2 family apoptosis regulator BOK) The protein encoded by this gene belongs to the BCL2 family, members of which form homo- or heterodimers, and act as anti- or proapoptotic regulators that are involved in a wide variety of cellular processes. Studies in rat show that this protein has restricted expression in reproductive tissues, interacts strongly with some antiapoptotic BCL2 proteins, not at all with proapoptotic BCL2 proteins, and induces apoptosis in transfected cells. Thus, this protein represents a proapoptotic member of the BCL2 family. [provided by RefSeq, Sep 2011]

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
BOKNM_032515.5 linkc.32C>T p.Ala11Val missense_variant Exon 2 of 5 ENST00000318407.5 NP_115904.1 Q9UMX3-1A0A024R4A8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BOKENST00000318407.5 linkc.32C>T p.Ala11Val missense_variant Exon 2 of 5 1 NM_032515.5 ENSP00000314132.3 Q9UMX3-1
BOKENST00000641230.1 linkn.55-2833C>T intron_variant Intron 1 of 1

Frequencies

GnomAD3 genomes
AF:
0.0000395
AC:
6
AN:
152078
Hom.:
0
Cov.:
33
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:
0.000193
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000422
AC:
57
AN:
1350472
Hom.:
1
Cov.:
31
AF XY:
0.0000479
AC XY:
32
AN XY:
668306
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000363
Gnomad4 SAS exome
AF:
0.000280
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000235
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000395
AC:
6
AN:
152078
Hom.:
0
Cov.:
33
AF XY:
0.0000404
AC XY:
3
AN XY:
74282
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
ExAC
AF:
0.0000437
AC:
5

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.32C>T (p.A11V) alteration is located in exon 2 (coding exon 1) of the BOK gene. This alteration results from a C to T substitution at nucleotide position 32, causing the alanine (A) at amino acid position 11 to be replaced by a valine (V). 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
0.91
BayesDel_addAF
Benign
-0.042
T
BayesDel_noAF
Benign
-0.30
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.20
T
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.33
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Uncertain
0.94
D
M_CAP
Uncertain
0.26
D
MetaRNN
Uncertain
0.45
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L
PrimateAI
Pathogenic
0.92
D
PROVEAN
Benign
-1.4
N
REVEL
Benign
0.20
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.51
MutPred
0.36
Gain of catalytic residue at A11 (P = 0.0148);
MVP
0.41
MPC
2.5
ClinPred
0.38
T
GERP RS
3.0
Varity_R
0.48
gMVP
0.62

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: rs758981632; hg19: chr2-242498930; API