chr7-16674412-A-G

Variant names:

• chr7-16674412-A-G
• NM_014038.3:c.59A>G

Variant summary

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

The NM_014038.3(BZW2):​c.59A>G​(p.Asp20Gly) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BZW2 NM_014038.3 missense, splice_region
• Scores: Splicing: ADA: 0.6847
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.32
• Publications: 0 publications found

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

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	c.59A>G	p.Asp20Gly	missense_variant, splice_region_variant	Exon 3 of 12	ENST00000258761.8	NP_054757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BZW2	ENST00000258761.8	c.59A>G	p.Asp20Gly	missense_variant, splice_region_variant	Exon 3 of 12	1	NM_014038.3	ENSP00000258761.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.59A>G (p.D20G) alteration is located in exon 3 (coding exon 2) of the BZW2 gene. This alteration results from a A to G substitution at nucleotide position 59, causing the aspartic acid (D) at amino acid position 20 to be replaced by a glycine (G). 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	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T;T;T;T;T;T;T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;.;D;D;D;D;D
M_CAP	Benign	0.068	D
MetaRNN	Uncertain	0.62	D;D;D;D;D;D;D
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.6	.;M;M;.;.;.;.
PhyloP100		9.3
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-5.4	D;D;D;.;D;D;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0030	D;D;D;.;D;D;D
Sift4G	Benign	0.074	T;T;T;T;T;T;T
Polyphen		0.99	D;P;P;.;.;.;.
Vest4		0.85, 0.85, 0.84
MutPred		0.30		Loss of ubiquitination at K24 (P = 0.0237);Loss of ubiquitination at K24 (P = 0.0237);Loss of ubiquitination at K24 (P = 0.0237);Loss of ubiquitination at K24 (P = 0.0237);Loss of ubiquitination at K24 (P = 0.0237);Loss of ubiquitination at K24 (P = 0.0237);Loss of ubiquitination at K24 (P = 0.0237);
MVP		0.50
MPC		0.93
ClinPred		0.99	D
GERP RS		6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.53
gMVP		0.74
Mutation Taster		=171/129	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.68
dbscSNV1_RF	Benign	0.66
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

Other links and lift over

hg19: chr7-16714037;