chr2-200812442-C-T

Variant names:

• chr2-200812442-C-T
• NM_001207067.2:c.-11+452C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001207068.3(BZW1):​c.35C>T​(p.Ala12Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000259 in 1,158,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000026 (0 hom.)
• Consequence: BZW1 NM_001207068.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.16
• Publications: 0 publications found

Genes affected

BZW1 (HGNC:18380): (basic leucine zipper and W2 domains 1) Enables RNA binding activity and cadherin binding activity. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

BZW1-AS1 (HGNC:40839): (BZW1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3190132).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001207068.3. 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
	BZW1	NM_001207067.2	MANE Select	c.-11+452C>T		intron	N/A	NP_001193996.1	Q7L1Q6-1
	BZW1	NM_001207068.3		c.35C>T	p.Ala12Val	missense	Exon 1 of 12	NP_001193997.1	Q7L1Q6-3
	BZW1	NM_001207069.2		c.2+133C>T		intron	N/A	NP_001193998.1	Q7L1Q6-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BZW1	ENST00000409600.6	TSL:1 MANE Select	c.-11+452C>T		intron	N/A	ENSP00000386474.1	Q7L1Q6-1
	BZW1	ENST00000460660.1	TSL:1	n.68+452C>T		intron	N/A
	BZW1	ENST00000452790.6	TSL:2	c.35C>T	p.Ala12Val	missense	Exon 1 of 12	ENSP00000394316.2	Q7L1Q6-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000259 AC: 3 AN: 1158416 Hom.: 0 Cov.: 30 AF XY: 0.00000539 AC XY: 3 AN XY: 556766

African (AFR) AF: 0.00 AC: 0 AN: 23720

American (AMR) AF: 0.00 AC: 0 AN: 12108

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16746

East Asian (EAS) AF: 0.00 AC: 0 AN: 27828

South Asian (SAS) AF: 0.00 AC: 0 AN: 41482

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25756

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3402

European-Non Finnish (NFE) AF: 0.00000312 AC: 3 AN: 960190

Other (OTH) AF: 0.00 AC: 0 AN: 47184

GnomAD4 genome Cov.: 33

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	0.13
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	18
DANN	Uncertain	1.0
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.022
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.55	T
M_CAP	Pathogenic	0.96	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.62	T
PhyloP100		3.2
PROVEAN	Benign	-0.070	N
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D
Vest4		0.28
MutPred		0.21		Gain of sheet (P = 0.0149)
MVP		0.46
MPC		0.94
ClinPred		0.98	D
GERP RS		4.8
PromoterAI		0.057	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
gMVP		0.23
Mutation Taster		=74/26	polymorphism

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

hg19: chr2-201677165;