14-74949297-C-G

Variant names:

• chr14-74949297-C-G
• rs2268614
• NM_002632.6:c.315+60G>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS2

The NM_002632.6(PGF):​c.315+60G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000423 in 1,182,834 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: PGF NM_002632.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.376
• Publications: 0 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]

LOC107984690 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002632.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGF	NM_002632.6	MANE Select	c.315+60G>C		intron	N/A	NP_002623.2
	PGF	NM_001293643.1		c.312+60G>C		intron	N/A	NP_001280572.1	Q86TW6
	PGF	NM_001207012.1		c.315+60G>C		intron	N/A	NP_001193941.1	P49763-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGF	ENST00000555567.6	TSL:1 MANE Select	c.315+60G>C		intron	N/A	ENSP00000451040.1	P49763-3
	PGF	ENST00000553716.5	TSL:1	c.315+60G>C		intron	N/A	ENSP00000451413.1	P49763-2
	PGF	ENST00000965660.1		c.315+60G>C		intron	N/A	ENSP00000635719.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000423 AC: 5 AN: 1182834 Hom.: 0 AF XY: 0.00000517 AC XY: 3 AN XY: 580192

African (AFR) AF: 0.00 AC: 0 AN: 25534

American (AMR) AF: 0.00 AC: 0 AN: 23332

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17388

East Asian (EAS) AF: 0.00 AC: 0 AN: 32274

South Asian (SAS) AF: 0.00 AC: 0 AN: 54564

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46442

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4778

European-Non Finnish (NFE) AF: 0.00000430 AC: 4 AN: 930342

Other (OTH) AF: 0.0000208 AC: 1 AN: 48180

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.2
DANN	Benign	0.79
PhyloP100		0.38

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

Other links and lift over

dbSNP: rs2268614; hg19: chr14-75416000;