rs2268613

Variant names:

• chr14-74941797-G-A
• rs2268613
• NM_002632.6:c.*909C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-74941797-G-A
• chr14-74941797-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000555567.6(PGF):​c.*909C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 152,474 control chromosomes in the GnomAD database, including 38,986 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 0.69 (38848 hom., cov: 31)
  • Exomes 𝑓: 0.77 (138 hom.)
• Consequence: PGF ENST00000555567.6 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17
• Publications: 15 publications found

Genes affected

PGF (HGNC:8893): (placental growth factor) Enables growth factor activity. Involved in positive regulation of cell population proliferation. Predicted to be located in extracellular region. Predicted to be active in extracellular space. Implicated in several diseases, including brain ischemia; diabetic neuropathy; glioblastoma; myocardial infarction; and pancreatic endocrine carcinoma. Biomarker of several diseases, including artery disease (multiple); autoimmune disease of musculoskeletal system (multiple); epilepsy (multiple); limited scleroderma; and pancreatic endocrine carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000555567.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGF	NM_002632.6	MANE Select	c.*909C>T		downstream_gene	N/A	NP_002623.2
	PGF	NM_001293643.1		c.*909C>T		downstream_gene	N/A	NP_001280572.1
	PGF	NM_001207012.1		c.*909C>T		downstream_gene	N/A	NP_001193941.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGF	ENST00000555567.6	TSL:1 MANE Select	c.*909C>T		downstream_gene	N/A	ENSP00000451040.1
	PGF	ENST00000553716.5	TSL:1	c.*909C>T		downstream_gene	N/A	ENSP00000451413.1
	PGF	ENST00000238607.10	TSL:3	c.*909C>T		downstream_gene	N/A	ENSP00000238607.6

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105584 AN: 151888 Hom.: 38853 Cov.: 31

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.865

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.729

GnomAD4 exome AF: 0.769 AC: 360 AN: 468 Hom.: 138 Cov.: 0 AF XY: 0.774 AC XY: 223 AN XY: 288

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.756 AC: 325 AN: 430

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 26 AN: 26

Other (OTH) AF: 0.667 AC: 4 AN: 6

GnomAD4 genome AF: 0.695 AC: 105597 AN: 152006 Hom.: 38848 Cov.: 31 AF XY: 0.695 AC XY: 51658 AN XY: 74298

African (AFR) AF: 0.436 AC: 18045 AN: 41416

American (AMR) AF: 0.776 AC: 11855 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.865 AC: 3002 AN: 3470

East Asian (EAS) AF: 0.851 AC: 4389 AN: 5156

South Asian (SAS) AF: 0.688 AC: 3308 AN: 4810

European-Finnish (FIN) AF: 0.742 AC: 7836 AN: 10560

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.803 AC: 54622 AN: 67996

Other (OTH) AF: 0.733 AC: 1550 AN: 2116

Alfa AF: 0.777 Hom.: 194753

Bravo AF: 0.687

Asia WGS AF: 0.742 AC: 2580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.11
DANN	Benign	0.65
PhyloP100		-2.2
Mutation Taster		=94/6	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs2268613; hg19: chr14-75408500;