7-77196856-C-T

Variant names:

• chr7-77196856-C-T
• rs773321059
• NM_006682.3:c.743G>A

Variant summary

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

The NM_006682.3(FGL2):​c.743G>A​(p.Gly248Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000948 in 1,613,888 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G248A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000096 (0 hom.)
• Consequence: FGL2 NM_006682.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.89
• Publications: 0 publications found

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]

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]

ACMG classification

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

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.743G>A	p.Gly248Glu	missense	Exon 2 of 2	NP_006673.1	Q14314
	CCDC146	NM_020879.3	MANE Select	c.156+29032C>T		intron	N/A	NP_065930.2	Q8IYE0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGL2	ENST00000248598.6	TSL:1 MANE Select	c.743G>A	p.Gly248Glu	missense	Exon 2 of 2	ENSP00000248598.5	Q14314
	CCDC146	ENST00000285871.5	TSL:1 MANE Select	c.156+29032C>T		intron	N/A	ENSP00000285871.4	Q8IYE0-1
	CCDC146	ENST00000890162.1		c.156+29032C>T		intron	N/A	ENSP00000560221.1

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152046 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

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: 0.000162

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000279 AC: 7 AN: 251160 AF XY: 0.0000221

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000617

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000965 AC: 141 AN: 1461842 Hom.: 0 Cov.: 32 AF XY: 0.0000894 AC XY: 65 AN XY: 727226

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000117 AC: 130 AN: 1111976

Other (OTH) AF: 0.000166 AC: 10 AN: 60396

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152046 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74248

African (AFR) AF: 0.0000242 AC: 1 AN: 41388

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000494 Hom.: 0

Bravo AF: 0.0000567

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Uncertain	0.64	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		3.9
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-6.6	D
REVEL	Pathogenic	0.73
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.97	D
Vest4		0.46
MVP		0.93
MPC		0.73
ClinPred		0.96	D
GERP RS		3.7
Varity_R		0.82
gMVP		0.88
Mutation Taster		=28/72	disease causing

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

Other links and lift over

dbSNP: rs773321059; hg19: chr7-76826173; COSMIC: COSV105065653; COSMIC: COSV105065653;