7-77196855-CC-AA

Variant names:

• chr7-77196855-CC-AA
• NM_006682.3:c.743_744delGGinsTT
• FGL2 p.Gly248Val

Variant summary

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

The NM_006682.3(FGL2):​c.743_744delGGinsTT​(p.Gly248Val) 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. G248E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FGL2 NM_006682.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.89
• Publications: 0 publications found

Genes affected

FGL2 (HGNC:3696): (fibrinogen like 2) The protein encoded by this gene is a secreted protein that is similar to the beta- and gamma-chains of fibrinogen. The carboxyl-terminus of the encoded protein consists of the fibrinogen-related domains (FRED). The encoded protein forms a tetrameric complex which is stabilized by interchain disulfide bonds. This protein may play a role in physiologic functions at mucosal sites. [provided by RefSeq, Jul 2008]

CCDC146 (HGNC:29296): (coiled-coil domain containing 146) Located in centriole. [provided by Alliance of Genome Resources, Apr 2022]

DTX2P1-UPK3BP1-PMS2P11 (HGNC:42360): (DTX2P1-UPK3BP1-PMS2P11 readthrough, transcribed pseudogene) This locus represents naturally-occurring readthrough transcription spanning multiple pseudogenes: DTX2P1 (DTX2 pseudogene 1), UPK3BP1 (uroplakin 3B pseudogene 1), PMS2P11 (PMS1 homolog 2, mismatch repair system component pseudogene 11). Some transcripts may also extend to PMS2P9 (PMS1 homolog 2, mismatch repair system component pseudogene 9). The readthrough transcripts likely do not encode functional proteins. [provided by RefSeq, Jan 2016]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006682.3. 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
	FGL2	NM_006682.3	MANE Select	c.743_744delGGinsTT	p.Gly248Val	missense	N/A	NP_006673.1	Q14314
	CCDC146	NM_020879.3	MANE Select	c.156+29031_156+29032delCCinsAA		intron	N/A	NP_065930.2	Q8IYE0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGL2	ENST00000248598.6	TSL:1 MANE Select	c.743_744delGGinsTT	p.Gly248Val	missense	N/A	ENSP00000248598.5	Q14314
	CCDC146	ENST00000285871.5	TSL:1 MANE Select	c.156+29031_156+29032delCCinsAA		intron	N/A	ENSP00000285871.4	Q8IYE0-1
	CCDC146	ENST00000890162.1		c.156+29031_156+29032delCCinsAA		intron	N/A	ENSP00000560221.1

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		3.9

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: chr7-76826172;