chr7-77199405-A-C

Position:

• chr7-77199405-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006682.3(FGL2):​c.389T>G​(p.Val130Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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)
• Consequence: FGL2 NM_006682.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.11

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]

FGL2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24649522).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGL2	NM_006682.3	c.389T>G	p.Val130Gly	missense_variant	1/2	ENST00000248598.6	NP_006673.1
CCDC146	NM_020879.3	c.156+31581A>C		intron_variant		ENST00000285871.5	NP_065930.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGL2	ENST00000248598.6	c.389T>G	p.Val130Gly	missense_variant	1/2	1	NM_006682.3	ENSP00000248598.5
CCDC146	ENST00000285871.5	c.156+31581A>C		intron_variant		1	NM_020879.3	ENSP00000285871.4
CCDC146	ENST00000415750.5	c.156+31581A>C		intron_variant		4		ENSP00000388649.1
FGL2	ENST00000637771.2	n.444T>G		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2024

The c.389T>G (p.V130G) alteration is located in exon 1 (coding exon 1) of the FGL2 gene. This alteration results from a T to G substitution at nucleotide position 389, causing the valine (V) at amino acid position 130 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T;T
Eigen	Benign	0.067
Eigen_PC	Benign	0.064
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.7	N;.
REVEL	Benign	0.16
Sift	Uncertain	0.0010	D;.
Sift4G	Benign	0.10	T;.
Polyphen		0.68	P;.
Vest4		0.49
MutPred		0.47		Loss of stability (P = 0.0037);Loss of stability (P = 0.0037);
MVP		0.77
MPC		0.38
ClinPred		0.94	D
GERP RS		6.2
Varity_R		0.37
gMVP		0.54

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-76828722;