chr7-16694971-G-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_014038.3(BZW2):​c.789G>T​(p.Gln263His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000113 in 1,591,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000090 ( 0 hom. )

Consequence

BZW2
NM_014038.3 missense

Scores

2
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.41
Variant links:
Genes affected
BZW2 (HGNC:18808): (basic leucine zipper and W2 domains 2) Enables cadherin binding activity. Predicted to be involved in cell differentiation and nervous system development. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.2432608).
BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BZW2NM_014038.3 linkuse as main transcriptc.789G>T p.Gln263His missense_variant 8/12 ENST00000258761.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BZW2ENST00000258761.8 linkuse as main transcriptc.789G>T p.Gln263His missense_variant 8/121 NM_014038.3 P1Q9Y6E2-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152206
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000200
AC:
5
AN:
249530
Hom.:
0
AF XY:
0.00000741
AC XY:
1
AN XY:
134956
show subpopulations
Gnomad AFR exome
AF:
0.000309
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000904
AC:
13
AN:
1438814
Hom.:
0
Cov.:
30
AF XY:
0.00000842
AC XY:
6
AN XY:
712680
show subpopulations
Gnomad4 AFR exome
AF:
0.000392
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:
0.0000329
AC:
5
AN:
152206
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.000121
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000831
ExAC
AF:
0.0000247
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 23, 2024The c.789G>T (p.Q263H) alteration is located in exon 8 (coding exon 7) of the BZW2 gene. This alteration results from a G to T substitution at nucleotide position 789, causing the glutamine (Q) at amino acid position 263 to be replaced by a histidine (H). 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
0.28
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.17
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.027
T;T;T;T;T;.;.
Eigen
Benign
-0.10
Eigen_PC
Benign
-0.065
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.93
D;.;D;D;D;D;D
M_CAP
Benign
0.052
D
MetaRNN
Benign
0.24
T;T;T;T;T;T;T
MetaSVM
Benign
-0.47
T
MutationAssessor
Benign
1.5
.;L;L;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-1.9
N;N;N;N;N;.;N
REVEL
Uncertain
0.38
Sift
Benign
0.14
T;T;T;T;T;.;T
Sift4G
Benign
0.12
T;T;T;T;T;T;T
Polyphen
0.70
P;P;P;.;.;.;.
Vest4
0.36, 0.36, 0.35, 0.34, 0.34
MutPred
0.27
Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);.;Loss of helix (P = 0.1299);.;.;
MVP
0.63
MPC
0.97
ClinPred
0.18
T
GERP RS
1.6
Varity_R
0.13
gMVP
0.47

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: rs760736472; hg19: chr7-16734596; API