dbSNP rs371407289: BZW2:p.Thr83Arg (chr7-16681313-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014038.3(BZW2):c.248C>G(p.Thr83Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,402 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T83M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

BZW2
NM_014038.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.91

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 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
BZW2	NM_014038.3 link	c.248C>G	p.Thr83Arg	missense_variant	Exon 4 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.248C>G	p.Thr83Arg	missense_variant	Exon 4 of 12	1	NM_014038.3	ENSP00000258761.3		Q9Y6E2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251112

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461402

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727044

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33462

American (AMR)

AF:

0.00

AC:

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111684

Other (OTH)

AF:

0.0000166

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.80

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.092

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

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.98

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

M_CAP

Benign

0.041

MetaRNN

Uncertain

0.43

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

MetaSVM

Benign

-0.70

MutationAssessor

Uncertain

2.4

.;M;M;.;.;.;.;.

PhyloP100

5.9

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.2

D;D;D;.;N;D;D;D

REVEL

Benign

0.15

Sift

Uncertain

0.0060

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

Sift4G

Uncertain

0.0070

D;D;D;D;D;D;D;D

Polyphen

0.74

P;P;P;.;.;.;.;.

Vest4

0.89, 0.89, 0.86, 0.88

MutPred

0.28

Loss of phosphorylation at T83 (P = 0.0343);Loss of phosphorylation at T83 (P = 0.0343);Loss of phosphorylation at T83 (P = 0.0343);Loss of phosphorylation at T83 (P = 0.0343);.;Loss of phosphorylation at T83 (P = 0.0343);Loss of phosphorylation at T83 (P = 0.0343);Loss of phosphorylation at T83 (P = 0.0343);

MVP

0.44

MPC

0.81

ClinPred

0.90

GERP RS

5.9

Varity_R

0.39

gMVP

0.79

Mutation Taster

=42/58

disease causing

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over