Variant 7-77199754-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006682.3(FGL2):c.40C>G(p.Leu14Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

FGL2
NM_006682.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.714

Variant links:

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]

FGL2 links:

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

CCDC146 links:

FGL2 (HGNC:):

FGL2 links:

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ACMG classification

Classification made for transcript

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=0.14378971).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGL2	NM_006682.3 linkuse as main transcript	c.40C>G	p.Leu14Val	missense_variant	1/2	ENST00000248598.6	NP_006673.1	Q14314A4D1B8
CCDC146	NM_020879.3 linkuse as main transcript	c.156+31930G>C		intron_variant		ENST00000285871.5	NP_065930.2	Q8IYE0-1Q96MS1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FGL2	ENST00000248598.6 linkuse as main transcript	c.40C>G	p.Leu14Val	missense_variant	1/2	1	NM_006682.3	ENSP00000248598.5	Q14314
CCDC146	ENST00000285871.5 linkuse as main transcript	c.156+31930G>C		intron_variant		1	NM_020879.3	ENSP00000285871.4	Q8IYE0-1
CCDC146	ENST00000415750.5 linkuse as main transcript	c.156+31930G>C		intron_variant		4		ENSP00000388649.1	C9JRR4
FGL2	ENST00000637771.2 linkuse as main transcript	n.95C>G		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

250458

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135368

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461758

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2024

The c.40C>G (p.L14V) alteration is located in exon 1 (coding exon 1) of the FGL2 gene. This alteration results from a C to G substitution at nucleotide position 40, causing the leucine (L) at amino acid position 14 to be replaced by a valine (V). 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

0.070

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.26

T;T

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.71

MutationAssessor

Benign

0.81

L;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.49

N;.

REVEL

Benign

0.037

Sift

Benign

0.032

D;.

Sift4G

Benign

0.16

T;.

Polyphen

0.30

B;.

Vest4

0.11

MutPred

0.34

Gain of catalytic residue at L14 (P = 0.0235);Gain of catalytic residue at L14 (P = 0.0235);

MVP

0.52

MPC

0.17

ClinPred

0.082

GERP RS

3.6

Varity_R

0.090

gMVP

0.47

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over