Genetic Variant NM_006682.3:c.818C>G (chr7-77196781-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006682.3(FGL2):c.818C>G(p.Ala273Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FGL2
NM_006682.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.704

Publications

0 publications found

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:

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]

DTX2P1-UPK3BP1-PMS2P11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17249331).

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.818C>G	p.Ala273Gly	missense	Exon 2 of 2	NP_006673.1	Q14314
	CCDC146	NM_020879.3	MANE Select	c.156+28957G>C		intron	N/A	NP_065930.2	Q8IYE0-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FGL2	ENST00000248598.6	TSL:1 MANE Select	c.818C>G	p.Ala273Gly	missense	Exon 2 of 2	ENSP00000248598.5	Q14314
CCDC146	ENST00000285871.5	TSL:1 MANE Select	c.156+28957G>C		intron	N/A	ENSP00000285871.4	Q8IYE0-1
CCDC146	ENST00000890162.1		c.156+28957G>C		intron	N/A	ENSP00000560221.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1112002

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

7.2

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.14

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.29

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.036

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.77

PhyloP100

0.70

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.80

REVEL

Benign

0.14

Sift

Benign

0.38

Sift4G

Benign

0.37

Polyphen

0.010

Vest4

0.11

MutPred

0.47

Gain of ubiquitination at K272 (P = 0.0716)

MVP

0.65

MPC

0.17

ClinPred

0.061

GERP RS

-2.0

Varity_R

0.044

gMVP

0.40

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over