chr7-16696952-A-T

Position:

• chr7-16696952-A-T

Variant summary

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

The NM_014038.3(BZW2):​c.860A>T​(p.Asp287Val) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BZW2 NM_014038.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.67

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]

(HGNC:):

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=0.24621677).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BZW2	NM_014038.3	c.860A>T	p.Asp287Val	missense_variant	9/12	ENST00000258761.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BZW2	ENST00000258761.8	c.860A>T	p.Asp287Val	missense_variant	9/12	1	NM_014038.3	P1
	ENST00000418907.1	n.439-872T>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Jan 16, 2024

The c.860A>T (p.D287V) alteration is located in exon 9 (coding exon 8) of the BZW2 gene. This alteration results from a A to T substitution at nucleotide position 860, causing the aspartic acid (D) at amino acid position 287 to be replaced by a valine (V). 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	0.18
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.058	T;T;T;T;.
Eigen	Benign	-0.083
Eigen_PC	Benign	0.098
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.95	D;.;D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.25	T;T;T;T;T
MetaSVM	Benign	-0.62	T
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.7	D;D;D;D;D
REVEL	Uncertain	0.32
Sift	Benign	0.042	D;T;T;D;D
Sift4G	Benign	0.32	T;T;T;T;D
Polyphen		0.0050	B;B;B;.;.
Vest4		0.31, 0.30, 0.31, 0.35
MutPred		0.39		Gain of catalytic residue at D287 (P = 0.0103);Gain of catalytic residue at D287 (P = 0.0103);Gain of catalytic residue at D287 (P = 0.0103);.;.;
MVP		0.66
MPC		0.81
ClinPred		0.66	D
GERP RS		3.4
Varity_R		0.13
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr7-16736577;