9-8331574-A-AAACTTACCATTCTTGAACTGTAACT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002839.4(PTPRD):c.5534+7_5534+8insAGTTACAGTTCAAGAATGGTAAGTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0451 in 1,606,216 control chromosomes in the GnomAD database, including 2,441 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.047 (209 hom., cov: 0)
  • Exomes 𝑓: 0.045 (2232 hom.)
• Consequence: PTPRD NM_002839.4 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.111

Genes affected

PTPRD (HGNC:9668): (protein tyrosine phosphatase receptor type D) 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 region, a single transmembrane segment and two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. The extracellular region of this protein is composed of three Ig-like and eight fibronectin type III-like domains. Studies of the similar genes in chicken and fly suggest the role of this PTP is in promoting neurite growth, and regulating neurons axon guidance. Multiple alternatively spliced transcript variants of this gene have been reported. A related pseudogene has been identified on chromosome 5. [provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 9-8331574-A-AAACTTACCATTCTTGAACTGTAACT is Benign according to our data. Variant chr9-8331574-A-AAACTTACCATTCTTGAACTGTAACT is described in ClinVar as [Benign]. Clinvar id is 227045.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRD	NM_002839.4	c.5534+7_5534+8insAGTTACAGTTCAAGAATGGTAAGTT		splice_region_variant, intron_variant		ENST00000381196.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRD	ENST00000381196.9	c.5534+7_5534+8insAGTTACAGTTCAAGAATGGTAAGTT		splice_region_variant, intron_variant		5	NM_002839.4	P1

Frequencies

GnomAD3 genomes AF: 0.0466 AC: 7082 AN: 151890 Hom.: 207 Cov.: 0

Gnomad AFR AF: 0.0423

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0517

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.0311

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.0469

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0419

Gnomad OTH AF: 0.0495

GnomAD4 exome AF: 0.0449 AC: 65343 AN: 1454212 Hom.: 2232 Cov.: 35 AF XY: 0.0481 AC XY: 34834 AN XY: 723618

Gnomad4 AFR exome AF: 0.0405

Gnomad4 AMR exome AF: 0.0543

Gnomad4 ASJ exome AF: 0.0335

Gnomad4 EAS exome AF: 0.0346

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.0471

Gnomad4 NFE exome AF: 0.0374

Gnomad4 OTH exome AF: 0.0508

GnomAD4 genome AF: 0.0468 AC: 7108 AN: 152004 Hom.: 209 Cov.: 0 AF XY: 0.0499 AC XY: 3707 AN XY: 74300

Gnomad4 AFR AF: 0.0427

Gnomad4 AMR AF: 0.0519

Gnomad4 ASJ AF: 0.0392

Gnomad4 EAS AF: 0.0312

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.0469

Gnomad4 NFE AF: 0.0419

Gnomad4 OTH AF: 0.0499

Alfa AF: 0.0328 Hom.: 255

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Apr 03, 2015

c.5534+7_5534+8ins25 in intron 44 of PTPRD: This variant is not expected to have clinical significance because it has been identified in 15% (2409/16470) South Asian chromosomes, including 184 homozygotes, by the Exome Aggregation Consortiu m Sequencing Project (http://exac.broadinstitute.org/variant/9-8331574-A-AAACTTA CCATTCTTGAACTGTAACT; dbSNP rs3215098). -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3215098; hg19: chr9-8331574;