9-8331574-A-AAACTTACCATTCTTGAACTGTAACT

Variant names:

• chr9-8331574-A-AAACTTACCATTCTTGAACTGTAACT
• rs3215098
• NM_002839.4:c.5534+7_5534+8insAGTTACAGTTCAAGAATGGTAAGTT

Variant summary

Our verdict is Benign. The variant received -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. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
PTPRD	NM_002839.4	c.5534+7_5534+8insAGTTACAGTTCAAGAATGGTAAGTT		splice_region_variant, intron_variant	Intron 44 of 45	ENST00000381196.9	NP_002830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRD	ENST00000381196.9	c.5534+7_5534+8insAGTTACAGTTCAAGAATGGTAAGTT		splice_region_variant, intron_variant	Intron 44 of 45	5	NM_002839.4	ENSP00000370593.3

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

African (AFR) AF: 0.0405 AC: 1353 AN: 33392

American (AMR) AF: 0.0543 AC: 2423 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.0335 AC: 874 AN: 26094

East Asian (EAS) AF: 0.0346 AC: 1371 AN: 39610

South Asian (SAS) AF: 0.139 AC: 11955 AN: 85800

European-Finnish (FIN) AF: 0.0471 AC: 2504 AN: 53144

Middle Eastern (MID) AF: 0.0794 AC: 455 AN: 5734

European-Non Finnish (NFE) AF: 0.0374 AC: 41357 AN: 1105766

Other (OTH) AF: 0.0508 AC: 3051 AN: 60088

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

African (AFR) AF: 0.0427 AC: 1769 AN: 41428

American (AMR) AF: 0.0519 AC: 791 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0392 AC: 136 AN: 3472

East Asian (EAS) AF: 0.0312 AC: 161 AN: 5162

South Asian (SAS) AF: 0.156 AC: 750 AN: 4816

European-Finnish (FIN) AF: 0.0469 AC: 497 AN: 10586

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0419 AC: 2846 AN: 67976

Other (OTH) AF: 0.0499 AC: 105 AN: 2104

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

Apr 03, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3215098; hg19: chr9-8331574; COSMIC: COSV61933755;