chr9-8331574-A-AAACTTACCCTTCTTGAACTGTAACT

Position:

• chr9-8331574-A-AAACTTACCCTTCTTGAACTGTAACT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002839.4(PTPRD):​c.5534+7_5534+8insAGTTACAGTTCAAGAAGGGTAAGTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: PTPRD NM_002839.4 splice_region, intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U: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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Oct 31, 2013

The 5534+7_5534+8ins25 variant in PTPRD has not been previously identified in individuals with familial angiolipomatosis. Data from large population studies is insufficient to assess the frequency of this variant. This variant results in an insertion of 25 bases into intron 44 and computational tools suggest the creation of an alternative 5' splice site downstream of the normal exon-intron boundary. However, this variant does not cause a change at the conserved (+1/+2) positions in the splice site consensus sequence and splice prediction tools do not suggest an impact to the canonical (normal) splice site. Therefore, it is not possible to predict whether this insertion will result in abnormal splicing without functional analysis. In summary, without additional studies, the clinical significance of this variant cannot be determined with certainty. -

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;