14-74941797-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002632.6(PGF):​c.*909C>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: PGF NM_002632.6 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGF	NM_002632.6	c.*909C>G		downstream_gene_variant		ENST00000555567.6	NP_002623.2
PGF	NM_001293643.1	c.*909C>G		downstream_gene_variant			NP_001280572.1
PGF	NM_001207012.1	c.*909C>G		downstream_gene_variant			NP_001193941.1
PGF	XM_047431476.1	c.*909C>G		downstream_gene_variant			XP_047287432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGF	ENST00000555567.6	c.*909C>G		downstream_gene_variant		1	NM_002632.6	ENSP00000451040.1
PGF	ENST00000553716.5	c.*909C>G		downstream_gene_variant		1		ENSP00000451413.1
PGF	ENST00000238607.10	c.*909C>G		downstream_gene_variant		3		ENSP00000238607.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.054
DANN	Benign	0.38
PhyloP100		-2.2

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;