Variant 1-96721870-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_021190.4(PTBP2):c.6C>A(p.Asp2Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PTBP2
NM_021190.4 missense, splice_region

Scores

Splicing: ADA: 0.3591

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.87

Variant links:

Genes affected

PTBP2 (HGNC:17662): (polypyrimidine tract binding protein 2) The protein encoded by this gene binds to intronic polypyrimidine clusters in pre-mRNA molecules and is implicated in controlling the assembly of other splicing-regulatory proteins. This protein is very similar to the polypyrimidine tract binding protein (PTB) but most of its isoforms are expressed primarily in the brain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

PTBP2 links:

PTBP2 (HGNC:):

PTBP2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27073032).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTBP2	NM_021190.4 linkuse as main transcript	c.6C>A	p.Asp2Glu	missense_variant, splice_region_variant	1/14	ENST00000674951.1	NP_067013.1	Q9UKA9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTBP2	ENST00000674951.1 linkuse as main transcript	c.6C>A	p.Asp2Glu	missense_variant, splice_region_variant	1/14		NM_021190.4	ENSP00000502818.1		Q9UKA9-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

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: AC0

AF:

0.00

AC:

AN:

1423070

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

703854

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152056

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 11, 2023

The c.6C>A (p.D2E) alteration is located in exon 1 (coding exon 1) of the PTBP2 gene. This alteration results from a C to A substitution at nucleotide position 6, causing the aspartic acid (D) at amino acid position 2 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.029

.;.;.;T

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.61

T;T;T;T

M_CAP

Pathogenic

0.53

MetaRNN

Benign

0.27

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;L;L;L

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.41

.;N;N;N

REVEL

Benign

0.023

Sift

Benign

0.30

.;T;T;T

Sift4G

Benign

0.75

T;T;T;T

Polyphen

0.021

B;B;B;B

Vest4

0.28

MutPred

0.28

Gain of disorder (P = 0.1319);Gain of disorder (P = 0.1319);Gain of disorder (P = 0.1319);Gain of disorder (P = 0.1319);

MVP

0.75

MPC

0.34

ClinPred

0.70

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.36

dbscSNV1_RF

Benign

0.57

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over