chr9-8331574-A-AAACTTACTTACCATTCTTGAACTGT

Variant names:

• chr9-8331574-A-AAACTTACTTACCATTCTTGAACTGT
• rs368394000
• NM_002839.4:c.5534+7_5534+8insACAGTTCAAGAATGGTAAGTAAGTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_002839.4(PTPRD):​c.5534+7_5534+8insACAGTTCAAGAATGGTAAGTAAGTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 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 0.013 (42 hom., cov: 0)
  • Exomes 𝑓: 0.0014 (56 hom.)
  • Failed GnomAD Quality Control
• Consequence: PTPRD NM_002839.4 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.111
• Publications: 1 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-AAACTTACTTACCATTCTTGAACTGT is Benign according to our data. Variant chr9-8331574-A-AAACTTACTTACCATTCTTGAACTGT is described in ClinVar as [Likely_benign]. Clinvar id is 2504285.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0129 (1966/152024) while in subpopulation AFR AF = 0.0439 (1817/41426). AF 95% confidence interval is 0.0422. There are 42 homozygotes in GnomAd4. There are 909 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1966 AD gene.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0129 AC: 1959 AN: 151908 Hom.: 43 Cov.: 0

Gnomad AFR AF: 0.0438

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00741

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00913

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00143 AC: 2084 AN: 1460110 Hom.: 56 Cov.: 35 AF XY: 0.00121 AC XY: 877 AN XY: 726472

African (AFR) AF: 0.0481 AC: 1607 AN: 33388

American (AMR) AF: 0.00379 AC: 169 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.0000813 AC: 7 AN: 86114

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53278

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5754

European-Non Finnish (NFE) AF: 0.0000954 AC: 106 AN: 1110876

Other (OTH) AF: 0.00302 AC: 182 AN: 60312

GnomAD4 genome AF: 0.0129 AC: 1966 AN: 152024 Hom.: 42 Cov.: 0 AF XY: 0.0122 AC XY: 909 AN XY: 74316

African (AFR) AF: 0.0439 AC: 1817 AN: 41426

American (AMR) AF: 0.00740 AC: 113 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 67982

Other (OTH) AF: 0.00903 AC: 19 AN: 2104

Alfa AF: 0.000567 Hom.: 0

Bravo AF: 0.0148

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 07, 2023

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Other links and lift over

dbSNP: rs368394000; hg19: chr9-8331574;