chr7-16685995-G-A

Variant summary

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

The NM_014038.3(BZW2):​c.496G>A​(p.Ala166Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000618 in 1,455,296 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: not found (cov: 30)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

BZW2
NM_014038.3 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.39
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=0.23458624).
BS2
High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BZW2NM_014038.3 linkuse as main transcriptc.496G>A p.Ala166Thr missense_variant 6/12 ENST00000258761.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BZW2ENST00000258761.8 linkuse as main transcriptc.496G>A p.Ala166Thr missense_variant 6/121 NM_014038.3 P1Q9Y6E2-1

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
AF:
0.00000618
AC:
9
AN:
1455296
Hom.:
0
Cov.:
36
AF XY:
0.00000553
AC XY:
4
AN XY:
723008
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000811
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
30
Alfa
AF:
0.0000330
Hom.:
0
ExAC
AF:
0.00000824
AC:
1

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 GeneticsFeb 23, 2023The c.496G>A (p.A166T) alteration is located in exon 6 (coding exon 5) of the BZW2 gene. This alteration results from a G to A substitution at nucleotide position 496, causing the alanine (A) at amino acid position 166 to be replaced by a threonine (T). 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
0.29
BayesDel_addAF
Benign
-0.051
T
BayesDel_noAF
Benign
-0.31
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.035
T;T;T;T;T;.;T
Eigen
Benign
0.15
Eigen_PC
Benign
0.22
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.96
D;.;D;D;D;D;D
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.23
T;T;T;T;T;T;T
MetaSVM
Benign
-0.86
T
MutationAssessor
Uncertain
2.3
.;M;M;.;.;.;.
MutationTaster
Benign
0.99
D;D;D;D
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-1.8
N;N;N;N;N;.;N
REVEL
Benign
0.11
Sift
Benign
0.083
T;T;T;T;T;.;T
Sift4G
Benign
0.066
T;T;T;T;T;T;T
Polyphen
0.20
B;B;B;.;.;.;.
Vest4
0.49, 0.49, 0.56
MVP
0.41
MPC
0.54
ClinPred
0.53
D
GERP RS
4.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.062
gMVP
0.37

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: rs762472281; hg19: chr7-16725620; COSMIC: COSV51755061; COSMIC: COSV51755061; API