8-56958288-T-C

Position:

• chr8-56958288-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017813.5(BPNT2):​c.*5505A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.885 in 152,188 control chromosomes in the GnomAD database, including 59,581 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.88 (59564 hom., cov: 31)
  • Exomes 𝑓: 0.97 (17 hom.)
• Consequence: BPNT2 NM_017813.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.45

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 8-56958288-T-C is Benign according to our data. Variant chr8-56958288-T-C is described in ClinVar as [Benign]. Clinvar id is 363327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPNT2	NM_017813.5	c.*5505A>G		3_prime_UTR_variant	5/5	ENST00000262644.9	NP_060283.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BPNT2	ENST00000262644	c.*5505A>G		3_prime_UTR_variant	5/5	1	NM_017813.5	ENSP00000262644.4

Frequencies

GnomAD3 genomes AF: 0.885 AC: 134486 AN: 152034 Hom.: 59518 Cov.: 31

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.929

Gnomad AMR AF: 0.920

Gnomad ASJ AF: 0.939

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.862

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.879

Gnomad OTH AF: 0.882

GnomAD4 exome AF: 0.972 AC: 35 AN: 36 Hom.: 17 Cov.: 0 AF XY: 0.967 AC XY: 29 AN XY: 30

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 NFE exome AF: 0.964

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.885 AC: 134590 AN: 152152 Hom.: 59564 Cov.: 31 AF XY: 0.884 AC XY: 65754 AN XY: 74374

Gnomad4 AFR AF: 0.884

Gnomad4 AMR AF: 0.920

Gnomad4 ASJ AF: 0.939

Gnomad4 EAS AF: 0.885

Gnomad4 SAS AF: 0.854

Gnomad4 FIN AF: 0.862

Gnomad4 NFE AF: 0.879

Gnomad4 OTH AF: 0.884

Alfa AF: 0.885 Hom.: 78121

Bravo AF: 0.890

Asia WGS AF: 0.883 AC: 3071 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

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Chondrodysplasia with joint dislocations, gPAPP type Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.62
DANN	Benign	0.54

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

LitVar

Other links and lift over

dbSNP: rs8718; hg19: chr8-57870847;