dbSNP rs759522830: FGL2:p.Leu14Phe (chr7-77199754-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_006682.3(FGL2):c.40C>T(p.Leu14Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L14V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FGL2
NM_006682.3 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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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=0.15571082).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGL2	NM_006682.3 link	c.40C>T	p.Leu14Phe	missense_variant	Exon 1 of 2	ENST00000248598.6	NP_006673.1	Q14314A4D1B8
CCDC146	NM_020879.3 link	c.156+31930G>A		intron_variant	Intron 2 of 18	ENST00000285871.5	NP_065930.2	Q8IYE0-1Q96MS1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FGL2	ENST00000248598.6 link	c.40C>T	p.Leu14Phe	missense_variant	Exon 1 of 2	1	NM_006682.3	ENSP00000248598.5	Q14314
CCDC146	ENST00000285871.5 link	c.156+31930G>A		intron_variant	Intron 2 of 18	1	NM_020879.3	ENSP00000285871.4	Q8IYE0-1
CCDC146	ENST00000415750.5 link	c.156+31930G>A		intron_variant	Intron 2 of 4	4		ENSP00000388649.1	C9JRR4
FGL2	ENST00000637771.2 link	n.95C>T		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250458

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135368

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461758

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727186

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

T;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.63

T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.74

MutationAssessor

Benign

0.81

L;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.2

N;.

REVEL

Benign

0.066

Sift

Uncertain

0.027

D;.

Sift4G

Uncertain

0.054

T;.

Polyphen

0.0060

B;.

Vest4

0.098

MutPred

0.41

Loss of solvent accessibility (P = 0.0509);Loss of solvent accessibility (P = 0.0509);

MVP

0.58

MPC

0.16

ClinPred

0.12

GERP RS

3.6

Varity_R

0.084

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over