rs117452684

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_017637.6(BNC2):c.2768C>T(p.Ala923Val) variant causes a missense change. The variant allele was found at a frequency of 0.0295 in 1,614,110 control chromosomes in the GnomAD database, including 848 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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. A923G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.019 ( 34 hom., cov: 31)

Exomes 𝑓: 0.031 ( 814 hom. )

Consequence

BNC2
NM_017637.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: 4.83

Publications

10 publications found

Variant links:

Genes affected

BNC2 (HGNC:30988): (basonuclin zinc finger protein 2) This gene encodes a conserved zinc finger protein. The encoded protein functions in skin color saturation. Mutations in this gene are associated with facial pigmented spots. This gene is also associated with susceptibility to adolescent idiopathic scoliosis. [provided by RefSeq, Jul 2016]

BNC2 Gene-Disease associations (from GenCC):

lower urinary tract obstruction, congenital
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
posterior urethral valve
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

BNC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004229605).

BP6

Variant 9-16419521-G-A is Benign according to our data. Variant chr9-16419521-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 120238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0193 (2941/152246) while in subpopulation NFE AF = 0.0323 (2199/68012). AF 95% confidence interval is 0.0312. There are 34 homozygotes in GnomAd4. There are 1341 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 34 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BNC2	NM_017637.6 link	c.2768C>T	p.Ala923Val	missense_variant	Exon 7 of 7	ENST00000380672.9	NP_060107.3	Q6ZN30-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BNC2	ENST00000380672.9 link	c.2768C>T	p.Ala923Val	missense_variant	Exon 7 of 7	2	NM_017637.6	ENSP00000370047.3		Q6ZN30-1

Frequencies

GnomAD3 genomes

AF:

0.0193

AC:

2943

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00545

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0166

Gnomad ASJ

AF:

0.0233

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00849

Gnomad FIN

AF:

0.00971

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0323

Gnomad OTH

AF:

0.0163

GnomAD2 exomes

AF:

0.0200

AC:

5022

AN:

250660

AF XY:

0.0205

show subpopulations

Gnomad AFR exome

AF:

0.00523

Gnomad AMR exome

AF:

0.0111

Gnomad ASJ exome

AF:

0.0195

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0111

Gnomad NFE exome

AF:

0.0333

Gnomad OTH exome

AF:

0.0189

GnomAD4 exome

AF:

0.0306

AC:

44667

AN:

1461864

Hom.:

814

Cov.:

AF XY:

0.0298

AC XY:

21702

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.00439

AC:

147

AN:

33480

American (AMR)

AF:

0.0112

AC:

500

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0220

AC:

574

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.00759

AC:

655

AN:

86258

European-Finnish (FIN)

AF:

0.0123

AC:

655

AN:

53418

Middle Eastern (MID)

AF:

0.00589

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0364

AC:

40507

AN:

1111984

Other (OTH)

AF:

0.0264

AC:

1592

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

2610

5220

7829

10439

13049

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1514

3028

4542

6056

7570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0193

AC:

2941

AN:

152246

Hom.:

Cov.:

AF XY:

0.0180

AC XY:

1341

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.00544

AC:

226

AN:

41570

American (AMR)

AF:

0.0165

AC:

253

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0233

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00829

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00971

AC:

103

AN:

10604

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0323

AC:

2199

AN:

68012

Other (OTH)

AF:

0.0161

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

150

301

451

602

752

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0290

Hom.:

238

Bravo

AF:

0.0190

TwinsUK

AF:

0.0353

AC:

131

ALSPAC

AF:

0.0381

AC:

147

ESP6500AA

AF:

0.00681

AC:

ESP6500EA

AF:

0.0341

AC:

293

ExAC

AF:

0.0209

AC:

2539

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0303

EpiControl

AF:

0.0304

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 24, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

BNC2: BP4, BS1, BS2 -

not specified

Benign:2

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 323/13006= 2.4% -

Aug 24, 2015

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

BNC2-related disorder

Benign:1

Jul 15, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Hypotension

Other:1

Centre for molecular medicine, Karolinska Institutet

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.069

T;T

Eigen

Benign

0.097

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.94

D;D

MetaRNN

Benign

0.0042

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;.

PhyloP100

4.8

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.33

N;N

REVEL

Benign

0.073

Sift

Benign

0.12

T;T

Sift4G

Benign

0.37

T;T

Polyphen

0.76

P;.

Vest4

0.24

MPC

0.13

ClinPred

0.014

GERP RS

5.5

Varity_R

0.080

gMVP

0.36

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over