Genetic Variant NM_014038.3:c.910G>A (chr7-16697002-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_014038.3(BZW2):c.910G>A(p.Ala304Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000242 in 1,614,024 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)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

BZW2
NM_014038.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.28

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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12860209).

BS2

High AC in GnomAdExome4 at 38 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014038.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BZW2	NM_014038.3	MANE Select	c.910G>A	p.Ala304Thr	missense	Exon 9 of 12	NP_054757.1	Q9Y6E2-1
BZW2	NM_001159767.2		c.910G>A	p.Ala304Thr	missense	Exon 9 of 12	NP_001153239.1	Q9Y6E2-1
BZW2	NM_001362717.2		c.910G>A	p.Ala304Thr	missense	Exon 9 of 12	NP_001349646.1	Q9Y6E2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BZW2	ENST00000258761.8	TSL:1 MANE Select	c.910G>A	p.Ala304Thr	missense	Exon 9 of 12	ENSP00000258761.3	Q9Y6E2-1
BZW2	ENST00000415365.5	TSL:1	c.910G>A	p.Ala304Thr	missense	Exon 9 of 11	ENSP00000403481.1	E7ETZ4
BZW2	ENST00000437745.5	TSL:1	n.*288G>A		non_coding_transcript_exon	Exon 8 of 11	ENSP00000406395.1	E9PFE3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152178

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000398

AC:

AN:

251226

AF XY:

0.0000442

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1461846

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000230

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000927

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000180

AC:

AN:

1111978

Other (OTH)

AF:

0.0000497

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41436

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000487

Hom.:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.028

Eigen

Benign

0.034

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.031

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.64

MutationAssessor

Benign

0.35

PhyloP100

5.3

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.68

REVEL

Uncertain

0.41

Sift

Benign

0.69

Sift4G

Benign

0.55

Polyphen

0.67

Vest4

0.21

MutPred

0.35

Loss of helix (P = 0.028)

MVP

0.28

MPC

0.55

ClinPred

0.085

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.55

Mutation Taster

=62/38

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over