chr7-16694930-C-A

Position:

• chr7-16694930-C-A

Variant summary

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

The NM_014038.3(BZW2):​c.748C>A​(p.Gln250Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BZW2 NM_014038.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.84

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BZW2	NM_014038.3	c.748C>A	p.Gln250Lys	missense_variant	8/12	ENST00000258761.8	NP_054757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BZW2	ENST00000258761.8	c.748C>A	p.Gln250Lys	missense_variant	8/12	1	NM_014038.3	ENSP00000258761	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1445894 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 717824

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Apr 15, 2024

The c.748C>A (p.Q250K) alteration is located in exon 8 (coding exon 7) of the BZW2 gene. This alteration results from a C to A substitution at nucleotide position 748, causing the glutamine (Q) at amino acid position 250 to be replaced by a lysine (K). 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	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T;T;T;T;T;.;.
Eigen	Uncertain	0.59
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D;.;D;D;D;D;D
M_CAP	Benign	0.053	D
MetaRNN	Uncertain	0.69	D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Benign	1.4	.;L;L;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.71	N;N;N;N;N;.;N
REVEL	Uncertain	0.43
Sift	Benign	0.39	T;T;T;T;T;.;T
Sift4G	Benign	0.67	T;T;T;T;T;T;T
Polyphen		0.92	P;P;P;.;.;.;.
Vest4		0.57, 0.57, 0.59, 0.64, 0.59
MutPred		0.43		Gain of MoRF binding (P = 0.0317);Gain of MoRF binding (P = 0.0317);Gain of MoRF binding (P = 0.0317);.;Gain of MoRF binding (P = 0.0317);.;.;
MVP		0.80
MPC		1.5
ClinPred		0.86	D
GERP RS		6.2
Varity_R		0.18
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1783432187; hg19: chr7-16734555;