NM_014038.3:c.748C>A

Variant names:

• chr7-16694930-C-A
• rs1783432187
• NM_014038.3:c.748C>A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• 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]

ENSG00000235837 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

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.748C>A	p.Gln250Lys	missense	Exon 8 of 12	NP_054757.1	Q9Y6E2-1
	BZW2	NM_001159767.2		c.748C>A	p.Gln250Lys	missense	Exon 8 of 12	NP_001153239.1	Q9Y6E2-1
	BZW2	NM_001362717.2		c.748C>A	p.Gln250Lys	missense	Exon 8 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.748C>A	p.Gln250Lys	missense	Exon 8 of 12	ENSP00000258761.3	Q9Y6E2-1
	BZW2	ENST00000415365.5	TSL:1	c.748C>A	p.Gln250Lys	missense	Exon 8 of 11	ENSP00000403481.1	E7ETZ4
	BZW2	ENST00000437745.5	TSL:1	n.*126C>A		non_coding_transcript_exon	Exon 7 of 11	ENSP00000406395.1	E9PFE3

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

African (AFR) AF: 0.00 AC: 0 AN: 33296

American (AMR) AF: 0.00 AC: 0 AN: 44566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25810

East Asian (EAS) AF: 0.00 AC: 0 AN: 39484

South Asian (SAS) AF: 0.00 AC: 0 AN: 84980

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53062

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099574

Other (OTH) AF: 0.00 AC: 0 AN: 59434

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	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
Eigen	Uncertain	0.59
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.053	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Benign	1.4	L
PhyloP100		7.8
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.71	N
REVEL	Uncertain	0.43
Sift	Benign	0.39	T
Sift4G	Benign	0.67	T
Polyphen		0.92	P
Vest4		0.57
MutPred		0.43		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
Mutation Taster		=36/64	disease causing

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

Other links and lift over

dbSNP: rs1783432187; hg19: chr7-16734555;