9-8331574-A-AAACTTACCATTCTTGAACTGT

Variant names:

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

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+8insACAGTTCAAGAATGGTAAGTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 1,605,656 control chromosomes in the GnomAD database, including 37,338 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (10516 hom., cov: 0)
  • Exomes 𝑓: 0.17 (26822 hom.)
• Consequence: PTPRD NM_002839.4 splice_region, intron
• Clinical Significance: Likely 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-AAACTTACCATTCTTGAACTGT is Benign according to our data. Variant chr9-8331574-A-AAACTTACCATTCTTGAACTGT is described in ClinVar as Likely_benign. ClinVar VariationId is 1317827.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 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+8insACAGTTCAAGAATGGTAAGTT		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+8insACAGTTCAAGAATGGTAAGTT		splice_region_variant, intron_variant	Intron 44 of 45	5	NM_002839.4	ENSP00000370593.3

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44911 AN: 151838 Hom.: 10494 Cov.: 0

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.278

GnomAD4 exome AF: 0.170 AC: 246601 AN: 1453702 Hom.: 26822 Cov.: 35 AF XY: 0.170 AC XY: 122778 AN XY: 723430

African (AFR) AF: 0.678 AC: 22583 AN: 33320

American (AMR) AF: 0.130 AC: 5805 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 6637 AN: 26022

East Asian (EAS) AF: 0.147 AC: 5840 AN: 39612

South Asian (SAS) AF: 0.198 AC: 16987 AN: 85988

European-Finnish (FIN) AF: 0.107 AC: 5711 AN: 53216

Middle Eastern (MID) AF: 0.270 AC: 1552 AN: 5740

European-Non Finnish (NFE) AF: 0.154 AC: 170188 AN: 1105072

Other (OTH) AF: 0.188 AC: 11298 AN: 60118

GnomAD4 genome AF: 0.296 AC: 44987 AN: 151954 Hom.: 10516 Cov.: 0 AF XY: 0.288 AC XY: 21389 AN XY: 74286

African (AFR) AF: 0.655 AC: 27134 AN: 41396

American (AMR) AF: 0.186 AC: 2831 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 904 AN: 3472

East Asian (EAS) AF: 0.118 AC: 611 AN: 5160

South Asian (SAS) AF: 0.199 AC: 956 AN: 4816

European-Finnish (FIN) AF: 0.103 AC: 1089 AN: 10590

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10600 AN: 67966

Other (OTH) AF: 0.278 AC: 585 AN: 2102

Alfa AF: 0.136 Hom.: 255

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 23, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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;