7-16685934-A-C

Position:

• chr7-16685934-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014038.3(BZW2):​c.435A>C​(p.Glu145Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
• Consequence: BZW2 NM_014038.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.07

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.115582705).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BZW2	NM_014038.3	c.435A>C	p.Glu145Asp	missense_variant	6/12	ENST00000258761.8	NP_054757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BZW2	ENST00000258761.8	c.435A>C	p.Glu145Asp	missense_variant	6/12	1	NM_014038.3	ENSP00000258761	P1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 07, 2024

The c.435A>C (p.E145D) alteration is located in exon 6 (coding exon 5) of the BZW2 gene. This alteration results from a A to C substitution at nucleotide position 435, causing the glutamic acid (E) at amino acid position 145 to be replaced by an aspartic acid (D). 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	0.094
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0081	T;T;T;T;T;T;T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.043
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.87	D;.;D;D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.12	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	.;L;L;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.29	N;N;N;N;N;N;N
REVEL	Benign	0.048
Sift	Benign	0.37	T;T;T;T;T;T;T
Sift4G	Benign	0.66	T;T;T;T;T;T;T
Polyphen		0.048	B;B;B;.;.;.;.
Vest4		0.34, 0.34, 0.36
MutPred		0.34		Gain of ubiquitination at K141 (P = 0.0804);Gain of ubiquitination at K141 (P = 0.0804);Gain of ubiquitination at K141 (P = 0.0804);.;Gain of ubiquitination at K141 (P = 0.0804);Gain of ubiquitination at K141 (P = 0.0804);Gain of ubiquitination at K141 (P = 0.0804);
MVP		0.39
MPC		0.47
ClinPred		0.47	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.048
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-16725559;