Variant chr7-77199199-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006682.3(FGL2):c.595C>G(p.Gln199Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,613,564 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

FGL2
NM_006682.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.342

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03191343).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGL2	NM_006682.3 link	c.595C>G	p.Gln199Glu	missense_variant	1/2	ENST00000248598.6	NP_006673.1	Q14314A4D1B8
CCDC146	NM_020879.3 link	c.156+31375G>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 link	c.595C>G	p.Gln199Glu	missense_variant	1/2	1	NM_006682.3	ENSP00000248598.5	Q14314
CCDC146	ENST00000285871.5 link	c.156+31375G>C		intron_variant		1	NM_020879.3	ENSP00000285871.4	Q8IYE0-1
CCDC146	ENST00000415750.5 link	c.156+31375G>C		intron_variant		4		ENSP00000388649.1	C9JRR4
FGL2	ENST00000637771.2 link	n.650C>G		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1461452

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727058

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000225

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152112

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

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

Oct 12, 2022

The c.595C>G (p.Q199E) 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 595, causing the glutamine (Q) at amino acid position 199 to be replaced by a glutamic acid (E). 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

0.059

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

6.9

DANN

Benign

0.69

DEOGEN2

Benign

0.18

T;T

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.57

T;T

M_CAP

Benign

0.0041

MetaRNN

Benign

0.032

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.16

N;.

REVEL

Benign

0.14

Sift

Benign

0.99

T;.

Sift4G

Benign

0.61

T;.

Polyphen

0.0

B;.

Vest4

0.060

MutPred

0.19

Gain of phosphorylation at S196 (P = 0.1062);Gain of phosphorylation at S196 (P = 0.1062);

MVP

0.30

MPC

0.16

ClinPred

0.031

GERP RS

1.9

Varity_R

0.069

gMVP

0.46

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