Genetic Variant BPNT2:c.*5689dupC (chr8-56958103-T-TG) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_017813.5(BPNT2):c.*5689dupC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 151,950 control chromosomes in the GnomAD database, including 30 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.015 ( 30 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BPNT2
NM_017813.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.341

Publications

0 publications found

Variant links:

Genes affected

BPNT2 (HGNC:26019): (3'(2'), 5'-bisphosphate nucleotidase 2) This gene encodes a member of the inositol monophosphatase family. The encoded protein is localized to the Golgi apparatus and catalyzes the hydrolysis of phosphoadenosine phosphate (PAP) to adenosine monophosphate (AMP). Mutations in this gene are a cause of GRAPP type chondrodysplasia with joint dislocations, and a pseudogene of this gene is located on the long arm of chromosome 1. [provided by RefSeq, Dec 2011]

BPNT2 Gene-Disease associations (from GenCC):

chondrodysplasia with joint dislocations, gPAPP type
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P

BPNT2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 8-56958103-T-TG is Benign according to our data. Variant chr8-56958103-T-TG is described in ClinVar as [Likely_benign]. Clinvar id is 363324.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0148 (2249/151950) while in subpopulation SAS AF = 0.0321 (154/4802). AF 95% confidence interval is 0.0279. There are 30 homozygotes in GnomAd4. There are 1050 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BPNT2	NM_017813.5 link	c.*5689dupC		3_prime_UTR_variant	Exon 5 of 5	ENST00000262644.9	NP_060283.3	Q9NX62A0A024R7W0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BPNT2	ENST00000262644.9 link	c.*5689dupC		3_prime_UTR_variant	Exon 5 of 5	1	NM_017813.5	ENSP00000262644.4		Q9NX62

Frequencies

GnomAD3 genomes

AF:

0.0148

AC:

2252

AN:

151834

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00395

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00965

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0318

Gnomad FIN

AF:

0.00993

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0239

Gnomad OTH

AF:

0.0187

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0148

AC:

2249

AN:

151950

Hom.:

Cov.:

AF XY:

0.0141

AC XY:

1050

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.00393

AC:

163

AN:

41428

American (AMR)

AF:

0.00964

AC:

147

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3466

East Asian (EAS)

AF:

0.00155

AC:

AN:

5168

South Asian (SAS)

AF:

0.0321

AC:

154

AN:

4802

European-Finnish (FIN)

AF:

0.00993

AC:

105

AN:

10576

Middle Eastern (MID)

AF:

0.0274

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0239

AC:

1622

AN:

67950

Other (OTH)

AF:

0.0176

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

103

206

308

411

514

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00188

Hom.:

Bravo

AF:

0.0140

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Chondrodysplasia

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.34

Mutation Taster

=100/0

polymorphism

(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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8-56958103-T-TG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over