2-200812420-C-A

Variant names:

• chr2-200812420-C-A
• rs986289477
• NM_001207067.2:c.-11+430C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001207068.3(BZW1):​c.13C>A​(p.Pro5Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P5L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BZW1 NM_001207068.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.908
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16052455).

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+430C>A		intron	N/A	NP_001193996.1	Q7L1Q6-1
	BZW1	NM_001207068.3		c.13C>A	p.Pro5Thr	missense	Exon 1 of 12	NP_001193997.1	Q7L1Q6-3
	BZW1	NM_001207069.2		c.2+111C>A		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+430C>A		intron	N/A	ENSP00000386474.1	Q7L1Q6-1
	BZW1	ENST00000460660.1	TSL:1	n.68+430C>A		intron	N/A
	BZW1	ENST00000452790.6	TSL:2	c.13C>A	p.Pro5Thr	missense	Exon 1 of 12	ENSP00000394316.2	Q7L1Q6-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1129678 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 539670

African (AFR) AF: 0.00 AC: 0 AN: 23176

American (AMR) AF: 0.00 AC: 0 AN: 9646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15472

East Asian (EAS) AF: 0.00 AC: 0 AN: 27044

South Asian (SAS) AF: 0.00 AC: 0 AN: 34500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3186

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 946392

Other (OTH) AF: 0.00 AC: 0 AN: 45962

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	15
DANN	Benign	0.90
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.27	T
M_CAP	Pathogenic	0.53	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.80	T
PhyloP100		0.91
PROVEAN	Benign	0.18	N
REVEL	Benign	0.20
Sift	Benign	0.044	D
Vest4		0.12
MutPred		0.16		Gain of phosphorylation at P5 (P = 0.0478)
MVP		0.26
MPC		1.8
ClinPred		0.86	D
GERP RS		4.1
PromoterAI		0.043	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
gMVP		0.24
Mutation Taster		=91/9	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

dbSNP: rs986289477; hg19: chr2-201677143;