NM_014038.3:c.202C>T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014038.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BZW2	NM_014038.3	MANE Select	c.202C>T	p.Leu68Phe	missense	Exon 3 of 12	NP_054757.1	Q9Y6E2-1
	BZW2	NM_001159767.2		c.202C>T	p.Leu68Phe	missense	Exon 3 of 12	NP_001153239.1	Q9Y6E2-1
	BZW2	NM_001362717.2		c.202C>T	p.Leu68Phe	missense	Exon 3 of 12	NP_001349646.1	Q9Y6E2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BZW2	ENST00000258761.8	TSL:1 MANE Select	c.202C>T	p.Leu68Phe	missense	Exon 3 of 12	ENSP00000258761.3	Q9Y6E2-1
	BZW2	ENST00000415365.5	TSL:1	c.202C>T	p.Leu68Phe	missense	Exon 3 of 11	ENSP00000403481.1	E7ETZ4
	BZW2	ENST00000437745.5	TSL:1	n.202C>T		non_coding_transcript_exon	Exon 3 of 11	ENSP00000406395.1	E9PFE3

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

African (AFR) AF: 0.00 AC: 0 AN: 33356

American (AMR) AF: 0.00 AC: 0 AN: 44206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25936

East Asian (EAS) AF: 0.00 AC: 0 AN: 39618

South Asian (SAS) AF: 0.00 AC: 0 AN: 84990

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53042

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.0000460 AC: 51 AN: 1108428

Other (OTH) AF: 0.0000499 AC: 3 AN: 60064

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000936 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.060	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	1.7	L
PhyloP100		7.9
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.44
Sift	Benign	0.067	T
Sift4G	Benign	0.065	T
Polyphen		1.0	D
Vest4		0.92
MVP		0.51
MPC		1.5
ClinPred		0.90	D
GERP RS		6.2
Varity_R		0.46
gMVP		0.75
Mutation Taster		=16/84	disease causing

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

Other links and lift over

dbSNP: rs1782709763; hg19: chr7-16714180;