rs2242045

Positions:

• chr7-137321061-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002825.7(PTN):​c.-2+22378C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 151,970 control chromosomes in the GnomAD database, including 13,082 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.39 (13082 hom., cov: 32)
• Consequence: PTN NM_002825.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.606

Genes affected

PTN (HGNC:9630): (pleiotrophin) The protein encoded by this gene is a secreted heparin-binding growth factor. The protein has significant roles in cell growth and survival, cell migration, angiogenesis and tumorigenesis. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Oct 2016]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTN	NM_002825.7	c.-2+22378C>T		intron_variant		ENST00000348225.7
PTN	NM_001321387.3	c.-2+22378C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTN	ENST00000348225.7	c.-2+22378C>T		intron_variant		1	NM_002825.7	P1
	ENST00000447529.1	n.266+2204G>A		intron_variant, non_coding_transcript_variant		2
PTN	ENST00000393083.2	c.-2+22378C>T		intron_variant		5
PTN	ENST00000699293.1	c.-2+22378C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59859 AN: 151852 Hom.: 13079 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.413

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.394 AC: 59859 AN: 151970 Hom.: 13082 Cov.: 32 AF XY: 0.392 AC XY: 29115 AN XY: 74256

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.498

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.539

Gnomad4 FIN AF: 0.459

Gnomad4 NFE AF: 0.496

Gnomad4 OTH AF: 0.411

Alfa AF: 0.467 Hom.: 32955

Bravo AF: 0.369

Asia WGS AF: 0.360 AC: 1254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	14
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2242045; hg19: chr7-137005808;