7-16674555-C-T

Variant names:

• chr7-16674555-C-T
• rs1782709763
• NM_014038.3:c.202C>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_014038.3(BZW2):​c.202C>T​(p.Leu68Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000371 in 1,455,368 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. L68L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000037 (0 hom.)
• Consequence: BZW2 NM_014038.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91

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 -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 54 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BZW2	NM_014038.3	c.202C>T	p.Leu68Phe	missense_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.202C>T	p.Leu68Phe	missense_variant	Exon 3 of 12	1	NM_014038.3	ENSP00000258761.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000371 AC: 54 AN: 1455368 Hom.: 0 Cov.: 30 AF XY: 0.0000401 AC XY: 29 AN XY: 723896

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: 0.0000460

Gnomad4 OTH exome AF: 0.0000499

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000936 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.202C>T (p.L68F) alteration is located in exon 3 (coding exon 2) of the BZW2 gene. This alteration results from a C to T substitution at nucleotide position 202, causing the leucine (L) at amino acid position 68 to be replaced by a phenylalanine (F). 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	0.88
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.069	T;T;T;T;T;T;T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;.;D;D;D;D;D
M_CAP	Benign	0.060	D
MetaRNN	Uncertain	0.65	D;D;D;D;D;D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	1.7	.;L;L;.;.;.;.
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-2.8	D;D;D;.;D;D;D
REVEL	Uncertain	0.44
Sift	Benign	0.067	T;T;T;.;T;T;T
Sift4G	Benign	0.065	T;T;T;T;D;T;T
Polyphen		1.0	D;D;D;.;.;.;.
Vest4		0.92, 0.92, 0.94
MVP		0.51
MPC		1.5
ClinPred		0.90	D
GERP RS		6.2
Varity_R		0.46
gMVP		0.75

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

LitVar

Other links and lift over

dbSNP: rs1782709763; hg19: chr7-16714180;