rs1377038665

Variant names:

• chr7-16685908-C-A
• rs1377038665
• NM_014038.3:c.409C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-16685908-C-A
• chr7-16685908-C-T

Variant summary

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

The NM_014038.3(BZW2):​c.409C>A​(p.Leu137Ile) variant causes a missense change involving the alteration of a conserved nucleotide. 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. L137F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000091 (0 hom., cov: 26)
  • Exomes 𝑓: 0.000015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BZW2 NM_014038.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.86
• Publications: 1 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 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BZW2	NM_014038.3	c.409C>A	p.Leu137Ile	missense_variant	Exon 6 of 12	ENST00000258761.8	NP_054757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BZW2	ENST00000258761.8	c.409C>A	p.Leu137Ile	missense_variant	Exon 6 of 12	1	NM_014038.3	ENSP00000258761.3

Frequencies

GnomAD3 genomes AF: 0.00000907 AC: 1 AN: 110314 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000297

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

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000149 AC: 16 AN: 1077220 Hom.: 0 Cov.: 36 AF XY: 0.0000133 AC XY: 7 AN XY: 526952

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 22848

American (AMR) AF: 0.00 AC: 0 AN: 27650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18172

East Asian (EAS) AF: 0.00 AC: 0 AN: 22736

South Asian (SAS) AF: 0.0000333 AC: 2 AN: 60086

European-Finnish (FIN) AF: 0.0000270 AC: 1 AN: 37028

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3778

European-Non Finnish (NFE) AF: 0.0000142 AC: 12 AN: 842232

Other (OTH) AF: 0.0000234 AC: 1 AN: 42690

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000906 AC: 1 AN: 110340 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 50724

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27706

American (AMR) AF: 0.00 AC: 0 AN: 8094

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3072

East Asian (EAS) AF: 0.000298 AC: 1 AN: 3354

South Asian (SAS) AF: 0.00 AC: 0 AN: 3210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3918

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 106

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 58610

Other (OTH) AF: 0.00 AC: 0 AN: 1450

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.083	T;T;T;T;T;T;T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	1.0	D;.;D;D;D;D;D
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.59	D;D;D;D;D;D;D
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.0	.;M;M;.;.;.;.
PhyloP100		7.9
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.5	N;N;N;N;N;N;N
REVEL	Benign	0.18
Sift	Benign	0.15	T;T;T;T;T;T;T
Sift4G	Benign	0.10	T;T;T;T;T;T;T
Polyphen		0.96	P;P;P;.;.;.;.
Vest4		0.68, 0.68, 0.73
MutPred		0.64		Gain of catalytic residue at L137 (P = 0.0413);Gain of catalytic residue at L137 (P = 0.0413);Gain of catalytic residue at L137 (P = 0.0413);.;Gain of catalytic residue at L137 (P = 0.0413);Gain of catalytic residue at L137 (P = 0.0413);Gain of catalytic residue at L137 (P = 0.0413);
MVP		0.44
MPC		0.67
ClinPred		0.90	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.53
Mutation Taster		=39/61	disease causing

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: rs1377038665; hg19: chr7-16725533;