2-200812420-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001207068.3(BZW1):​c.13C>G​(p.Pro5Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000133 in 1,282,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). 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: 𝑓 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000053 (0 hom.)
• Consequence: BZW1 NM_001207068.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06879297).
• BP6: Variant 2-200812420-C-G is Benign according to our data. Variant chr2-200812420-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2215119.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 11 AD gene.

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>G		intron	N/A	NP_001193996.1	Q7L1Q6-1
	BZW1	NM_001207068.3		c.13C>G	p.Pro5Ala	missense	Exon 1 of 12	NP_001193997.1	Q7L1Q6-3
	BZW1	NM_001207069.2		c.2+111C>G		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>G		intron	N/A	ENSP00000386474.1	Q7L1Q6-1
	BZW1	ENST00000460660.1	TSL:1	n.68+430C>G		intron	N/A
	BZW1	ENST00000452790.6	TSL:2	c.13C>G	p.Pro5Ala	missense	Exon 1 of 12	ENSP00000394316.2	Q7L1Q6-3

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152228 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 5502 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000531 AC: 6 AN: 1129680 Hom.: 0 Cov.: 30 AF XY: 0.00000741 AC XY: 4 AN XY: 539672

African (AFR) AF: 0.000216 AC: 5 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: 34502

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: 0.0000218 AC: 1 AN: 45962

GnomAD4 genome AF: 0.0000722 AC: 11 AN: 152342 Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2 AN XY: 74496

African (AFR) AF: 0.000265 AC: 11 AN: 41586

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000945

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.043
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	15
DANN	Benign	0.81
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.0086	N
LIST_S2	Benign	0.26	T
M_CAP	Pathogenic	0.44	D
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-0.99	T
PhyloP100		0.91
PROVEAN	Benign	0.15	N
REVEL	Benign	0.15
Sift	Benign	1.0	T
Vest4		0.11
MutPred		0.19		Loss of relative solvent accessibility (P = 0.0071)
MVP		0.20
MPC		1.5
ClinPred		0.50	T
GERP RS		4.1
PromoterAI		0.065	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
gMVP		0.12
Mutation Taster		=97/3	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;