Genetic Variant BZW2:p.Ala166Ser (chr7-16685995-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014038.3(BZW2):c.496G>T(p.Ala166Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000671 in 149,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A166T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BZW2
NM_014038.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.39

Publications

2 publications found

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]

BZW2 links:

ENSG00000235837 (HGNC:):

ENSG00000235837 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2203156).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BZW2	NM_014038.3 link	c.496G>T	p.Ala166Ser	missense_variant	Exon 6 of 12	ENST00000258761.8	NP_054757.1	Q9Y6E2-1A0A024RA42

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BZW2	ENST00000258761.8 link	c.496G>T	p.Ala166Ser	missense_variant	Exon 6 of 12	1	NM_014038.3	ENSP00000258761.3		Q9Y6E2-1

Frequencies

GnomAD3 genomes

AF:

0.00000671

AC:

AN:

149004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1455296

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723008

African (AFR)

AF:

0.00

AC:

AN:

33418

American (AMR)

AF:

0.00

AC:

AN:

44030

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25878

East Asian (EAS)

AF:

0.00

AC:

AN:

39546

South Asian (SAS)

AF:

0.00

AC:

AN:

84406

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52830

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109248

Other (OTH)

AF:

0.00

AC:

AN:

60186

GnomAD4 genome

AF:

0.00000671

AC:

AN:

149004

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72468

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40282

American (AMR)

AF:

0.00

AC:

AN:

14684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3452

East Asian (EAS)

AF:

0.00

AC:

AN:

4992

South Asian (SAS)

AF:

0.00

AC:

AN:

4694

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9950

Middle Eastern (MID)

AF:

0.00

AC:

AN:

300

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67710

Other (OTH)

AF:

0.00

AC:

AN:

2028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.024

T;T;T;T;T;.;T

Eigen

Benign

-0.12

Eigen_PC

Benign

0.026

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

D;.;D;D;D;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.22

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

.;L;L;.;.;.;.

PhyloP100

5.4

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.2

N;N;N;N;N;.;N

REVEL

Benign

0.072

Sift

Benign

0.26

T;T;T;T;T;.;T

Sift4G

Benign

0.34

T;T;T;T;T;T;T

Polyphen

0.0010

B;B;B;.;.;.;.

Vest4

0.29, 0.29, 0.29, 0.33

MutPred

0.48

Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);.;Gain of relative solvent accessibility (P = 0.09);.;Gain of relative solvent accessibility (P = 0.09);

MVP

0.44

MPC

0.48

ClinPred

0.69

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.060

gMVP

0.30

Mutation Taster

=89/11

polymorphism

(source)

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

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7-16685995-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over