chr2-200820013-C-G

Variant names:

• chr2-200820013-C-G
• rs765964327
• NM_001207067.2:c.998C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001207067.2(BZW1):​c.998C>G​(p.Thr333Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000254 in 1,536,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: BZW1 NM_001207067.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.06
• 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]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1736255).
• BS2: High AC in GnomAd4 at 7 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001207067.2. 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.998C>G	p.Thr333Ser	missense	Exon 10 of 12	NP_001193996.1	Q7L1Q6-1
	BZW1	NM_001207068.3		c.1094C>G	p.Thr365Ser	missense	Exon 10 of 12	NP_001193997.1	Q7L1Q6-3
	BZW1	NM_001207069.2		c.1010C>G	p.Thr337Ser	missense	Exon 10 of 12	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.998C>G	p.Thr333Ser	missense	Exon 10 of 12	ENSP00000386474.1	Q7L1Q6-1
	BZW1	ENST00000452790.6	TSL:2	c.1094C>G	p.Thr365Ser	missense	Exon 10 of 12	ENSP00000394316.2	Q7L1Q6-3
	BZW1	ENST00000409226.5	TSL:2	c.1010C>G	p.Thr337Ser	missense	Exon 10 of 12	ENSP00000386837.1	Q7L1Q6-4

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152212 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

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: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000661 AC: 1 AN: 151308 AF XY: 0.0000126

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: 0.0000165

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000231 AC: 32 AN: 1383856 Hom.: 0 Cov.: 30 AF XY: 0.0000205 AC XY: 14 AN XY: 681302

African (AFR) AF: 0.00 AC: 0 AN: 30972

American (AMR) AF: 0.00 AC: 0 AN: 32972

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24676

East Asian (EAS) AF: 0.00 AC: 0 AN: 35624

South Asian (SAS) AF: 0.00 AC: 0 AN: 76540

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49448

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4382

European-Non Finnish (NFE) AF: 0.0000299 AC: 32 AN: 1071840

Other (OTH) AF: 0.00 AC: 0 AN: 57402

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152212 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74368

African (AFR) AF: 0.0000483 AC: 2 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.00000917 AC: 1

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	0.067
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Benign	0.91
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.066
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	0.29	N
PhyloP100		6.1
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.0	N
REVEL	Uncertain	0.31
Sift	Benign	0.76	T
Sift4G	Benign	0.67	T
Polyphen		0.0020	B
Vest4		0.15
MutPred		0.35		Gain of disorder (P = 0.0407)
MVP		0.51
MPC		0.86
ClinPred		0.24	T
GERP RS		5.8
Varity_R		0.13
gMVP		0.069
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs765964327; hg19: chr2-201684736;