chr2-75664678-A-C

Variant names:

• chr2-75664678-A-C
• NM_003203.5:c.2334T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003203.5(GCFC2):​c.2334T>G​(p.Ile778Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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)
• Consequence: GCFC2 NM_003203.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.481
• Publications: 0 publications found

Genes affected

GCFC2 (HGNC:1317): (GC-rich sequence DNA-binding factor 2) The first mRNA transcript isolated for this gene was part of an artificial chimera derived from two distinct gene transcripts and a primer used in the cloning process (see Genbank accession M29204). A positively charged amino terminus present only in the chimera was determined to bind GC-rich DNA, thus mistakenly thought to identify a transcription factor gene. [provided by RefSeq, Jul 2008]

MRPL19 (HGNC:14052): (mitochondrial ribosomal protein L19) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein. [provided by RefSeq, Jul 2008]

ACMG classification

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=0.1000652).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003203.5. 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
	GCFC2	NM_003203.5	MANE Select	c.2334T>G	p.Ile778Met	missense	Exon 17 of 17	NP_003194.3
	GCFC2	NM_001410845.1		c.2220T>G	p.Ile740Met	missense	Exon 17 of 17	NP_001397774.1	P16383-2
	GCFC2	NM_001201334.2		c.1827T>G	p.Ile609Met	missense	Exon 17 of 17	NP_001188263.1	B3KUM5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCFC2	ENST00000321027.8	TSL:1 MANE Select	c.2334T>G	p.Ile778Met	missense	Exon 17 of 17	ENSP00000318690.3	P16383-1
	GCFC2	ENST00000470197.5	TSL:1	n.1676T>G		non_coding_transcript_exon	Exon 13 of 13
	GCFC2	ENST00000884726.1		c.2358T>G	p.Ile786Met	missense	Exon 17 of 17	ENSP00000554785.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 17

GnomAD4 genome Cov.: 32

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	0.081
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.053	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.48
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.037
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.72	P
Vest4		0.27
MutPred		0.24		Loss of stability (P = 0.0322)
MVP		0.62
MPC		0.28
ClinPred		0.46	T
GERP RS		0.37
Varity_R		0.074
gMVP		0.32
Mutation Taster		=99/1	polymorphism

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

hg19: chr2-75891804;