5-76617828-ATC-GTT

Variant names:

• chr5-76617828-ATC-GTT
• NM_004101.4:c.877_879delGATinsAAC
• F2RL2 p.Asp293Asn

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_004101.4(F2RL2):​c.877_879delGATinsAAC​(p.Asp293Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D293Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: F2RL2 NM_004101.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.58
• Publications: 0 publications found

Genes affected

F2RL2 (HGNC:3539): (coagulation factor II thrombin receptor like 2) This gene encodes a member of the protease-activated receptor (PAR) family which is a subfamily of the seven transmembrane G protein-coupled cell surface receptor family. The encoded protein acts as a cofactor in the thrombin-mediated cleavage and activation of the protease-activated receptor family member PAR4. The encoded protein plays an essential role in hemostasis and thrombosis. Alternate splicing results in multiple transcript variants that encode different isoforms. [provided by RefSeq, Feb 2012]

IQGAP2 (HGNC:6111): (IQ motif containing GTPase activating protein 2) This gene encodes a member of the IQGAP family. The encoded protein contains three IQ domains, one calponin homology domain, one Ras-GAP domain and one WW domain. This protein interacts with components of the cytoskeleton, with cell adhesion molecules, and with several signaling molecules to regulate cell morphology and motility. It also acts as a tumor suppressor and has been found to play a role in regulating innate antiviral responses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004101.4. 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
	F2RL2	NM_004101.4	MANE Select	c.877_879delGATinsAAC	p.Asp293Asn	missense	N/A	NP_004092.1	O00254-1
	IQGAP2	NM_006633.5	MANE Select	c.1521+6645_1521+6647delATCinsGTT		intron	N/A	NP_006624.3	Q13576-1
	F2RL2	NM_001256566.2		c.811_813delGATinsAAC	p.Asp271Asn	missense	N/A	NP_001243495.1	O00254-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F2RL2	ENST00000296641.5	TSL:1 MANE Select	c.877_879delGATinsAAC	p.Asp293Asn	missense	N/A	ENSP00000296641.3	O00254-1
	IQGAP2	ENST00000274364.11	TSL:1 MANE Select	c.1521+6645_1521+6647delATCinsGTT		intron	N/A	ENSP00000274364.6	Q13576-1
	IQGAP2	ENST00000396234.7	TSL:1	c.180+6645_180+6647delATCinsGTT		intron	N/A	ENSP00000379535.3	Q13576-2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.6

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-75913653;