chr7-16694846-G-A

Position:

• chr7-16694846-G-A

Variant summary

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

The NM_014038.3(BZW2):​c.664G>A​(p.Val222Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000146 in 1,367,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: BZW2 NM_014038.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.61

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=0.24793899).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BZW2	NM_014038.3	c.664G>A	p.Val222Ile	missense_variant	8/12	ENST00000258761.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BZW2	ENST00000258761.8	c.664G>A	p.Val222Ile	missense_variant	8/12	1	NM_014038.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1367528 Hom.: 0 Cov.: 30 AF XY: 0.00000297 AC XY: 2 AN XY: 672658

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: 0.00000191

Gnomad4 OTH exome AF: 0.00

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

Dec 27, 2023

The c.664G>A (p.V222I) alteration is located in exon 8 (coding exon 7) of the BZW2 gene. This alteration results from a G to A substitution at nucleotide position 664, causing the valine (V) at amino acid position 222 to be replaced by an isoleucine (I). 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	0.084
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.0042	T;T;T;T;T;.;.
Eigen	Benign	0.075
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D;.;D;D;D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.25	T;T;T;T;T;T;T
MetaSVM	Benign	-0.51	T
MutationTaster	Benign	0.79	D;D;D;D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.31	N;N;N;N;N;.;N
REVEL	Benign	0.23
Sift	Benign	0.65	T;T;T;T;T;.;T
Sift4G	Benign	0.62	T;T;T;T;T;T;T
Polyphen		0.0040	B;B;B;.;.;.;.
Vest4		0.16, 0.15, 0.14, 0.12
MutPred		0.32		Gain of helix (P = 0.2684);Gain of helix (P = 0.2684);Gain of helix (P = 0.2684);.;Gain of helix (P = 0.2684);.;.;
MVP		0.40
MPC		0.43
ClinPred		0.58	D
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.050
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr7-16734471;