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GeneBe

20-2986784-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001385305.1(PTPRA):c.462G>A(p.Ala154=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00276 in 1,612,770 control chromosomes in the GnomAD database, including 111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0042 ( 10 hom., cov: 32)
Exomes 𝑓: 0.0026 ( 101 hom. )

Consequence

PTPRA
NM_001385305.1 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0850
Variant links:
Genes affected
PTPRA (HGNC:9664): (protein tyrosine phosphatase receptor type A) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains an extracellular domain, a single transmembrane segment and two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. This PTP has been shown to dephosphorylate and activate Src family tyrosine kinases, and is implicated in the regulation of integrin signaling, cell adhesion and proliferation. Three alternatively spliced variants of this gene, which encode two distinct isoforms, have been reported. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 20-2986784-G-A is Benign according to our data. Variant chr20-2986784-G-A is described in ClinVar as [Benign]. Clinvar id is 788920.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.085 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00422 (643/152226) while in subpopulation AMR AF= 0.0289 (441/15284). AF 95% confidence interval is 0.0266. There are 10 homozygotes in gnomad4. There are 361 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 642 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PTPRANM_001385305.1 linkuse as main transcriptc.462G>A p.Ala154= synonymous_variant 7/24 ENST00000399903.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PTPRAENST00000399903.7 linkuse as main transcriptc.462G>A p.Ala154= synonymous_variant 7/245 NM_001385305.1 P4P18433-5

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00422
AC:
642
AN:
152108
Hom.:
10
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00101
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0288
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0280
Gnomad SAS
AF:
0.000828
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00978
AC:
2460
AN:
251434
Hom.:
72
AF XY:
0.00773
AC XY:
1050
AN XY:
135890
show subpopulations
Gnomad AFR exome
AF:
0.000984
Gnomad AMR exome
AF:
0.0534
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0298
Gnomad SAS exome
AF:
0.000621
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000616
Gnomad OTH exome
AF:
0.00342
GnomAD4 exome
AF:
0.00261
AC:
3814
AN:
1460544
Hom.:
101
Cov.:
30
AF XY:
0.00232
AC XY:
1683
AN XY:
726702
show subpopulations
Gnomad4 AFR exome
AF:
0.000389
Gnomad4 AMR exome
AF:
0.0490
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0353
Gnomad4 SAS exome
AF:
0.000638
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000261
Gnomad4 OTH exome
AF:
0.00204
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00422
AC:
643
AN:
152226
Hom.:
10
Cov.:
32
AF XY:
0.00485
AC XY:
361
AN XY:
74422
show subpopulations
Gnomad4 AFR
AF:
0.00101
Gnomad4 AMR
AF:
0.0289
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0278
Gnomad4 SAS
AF:
0.000829
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00236
Alfa
AF:
0.000608
Hom.:
0
Bravo
AF:
0.00722
Asia WGS
AF:
0.0110
AC:
37
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeAug 14, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.49
Cadd
Benign
12
Dann
Benign
0.81
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
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.

Other links and lift over

dbSNP: rs78716368; hg19: chr20-2967430; COSMIC: COSV53782179; API