7-16694965-G-T

Variant names:

• chr7-16694965-G-T
• NM_014038.3:c.783G>T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NM_014038.3(BZW2):​c.783G>T​(p.Glu261Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000139 in 1,440,134 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: not found (cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: BZW2 NM_014038.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.338

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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.40287203).
• BS2: High AC in GnomAdExome4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BZW2	NM_014038.3	c.783G>T	p.Glu261Asp	missense_variant	Exon 8 of 12	ENST00000258761.8	NP_054757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BZW2	ENST00000258761.8	c.783G>T	p.Glu261Asp	missense_variant	Exon 8 of 12	1	NM_014038.3	ENSP00000258761.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000139 AC: 20 AN: 1440134 Hom.: 0 Cov.: 30 AF XY: 0.0000140 AC XY: 10 AN XY: 713662

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000183

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.783G>T (p.E261D) alteration is located in exon 8 (coding exon 7) of the BZW2 gene. This alteration results from a G to T substitution at nucleotide position 783, causing the glutamic acid (E) at amino acid position 261 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	0.15
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T;T;T;T;T;.;.
Eigen	Benign	0.092
Eigen_PC	Benign	0.052
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.86	D;.;D;D;D;D;D
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.40	T;T;T;T;T;T;T
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	1.7	.;L;L;.;.;.;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.6	N;N;N;N;N;.;N
REVEL	Uncertain	0.44
Sift	Benign	0.15	T;T;T;T;T;.;T
Sift4G	Benign	0.39	T;T;T;T;T;T;T
Polyphen		0.98	D;D;D;.;.;.;.
Vest4		0.38, 0.38, 0.39, 0.37, 0.36
MutPred		0.30		Loss of ubiquitination at K256 (P = 0.0683);Loss of ubiquitination at K256 (P = 0.0683);Loss of ubiquitination at K256 (P = 0.0683);.;Loss of ubiquitination at K256 (P = 0.0683);.;.;
MVP		0.63
MPC		1.3
ClinPred		0.91	D
GERP RS		-0.92
Varity_R		0.30
gMVP		0.50

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: chr7-16734590;