2-75679846-G-A

Variant names:

• chr2-75679846-G-A
• rs4853169
• NM_003203.5:c.1812+347C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003203.5(GCFC2):​c.1812+347C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 406,642 control chromosomes in the GnomAD database, including 10,620 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (3481 hom., cov: 33)
  • Exomes 𝑓: 0.23 (7139 hom.)
• Consequence: GCFC2 NM_003203.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257
• Publications: 24 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]

LOC124906025 (HGNC:):

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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCFC2	NM_003203.5	c.1812+347C>T		intron_variant	Intron 12 of 16	ENST00000321027.8	NP_003194.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCFC2	ENST00000321027.8	c.1812+347C>T		intron_variant	Intron 12 of 16	1	NM_003203.5	ENSP00000318690.3

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29129 AN: 152014 Hom.: 3476 Cov.: 33

Gnomad AFR AF: 0.0533

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.182

GnomAD2 exomes AF: 0.193 AC: 280 AN: 1450 AF XY: 0.194

Gnomad AFR exome AF: 0.0667

Gnomad AMR exome AF: 0.268

Gnomad ASJ exome AF: 0.183

Gnomad EAS exome AF: 0.101

Gnomad FIN exome AF: 0.222

Gnomad NFE exome AF: 0.192

Gnomad OTH exome AF: 0.238

GnomAD4 exome AF: 0.229 AC: 58265 AN: 254510 Hom.: 7139 Cov.: 0 AF XY: 0.230 AC XY: 29679 AN XY: 129174

African (AFR) AF: 0.0565 AC: 408 AN: 7224

American (AMR) AF: 0.234 AC: 1919 AN: 8212

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 1898 AN: 9402

East Asian (EAS) AF: 0.129 AC: 3007 AN: 23250

South Asian (SAS) AF: 0.262 AC: 996 AN: 3798

European-Finnish (FIN) AF: 0.290 AC: 6130 AN: 21172

Middle Eastern (MID) AF: 0.173 AC: 227 AN: 1314

European-Non Finnish (NFE) AF: 0.246 AC: 40255 AN: 163370

Other (OTH) AF: 0.204 AC: 3425 AN: 16768

GnomAD4 genome AF: 0.192 AC: 29143 AN: 152132 Hom.: 3481 Cov.: 33 AF XY: 0.193 AC XY: 14362 AN XY: 74356

African (AFR) AF: 0.0532 AC: 2212 AN: 41540

American (AMR) AF: 0.206 AC: 3154 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 718 AN: 3466

East Asian (EAS) AF: 0.150 AC: 779 AN: 5180

South Asian (SAS) AF: 0.272 AC: 1308 AN: 4816

European-Finnish (FIN) AF: 0.297 AC: 3141 AN: 10574

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17218 AN: 67956

Other (OTH) AF: 0.181 AC: 381 AN: 2110

Alfa AF: 0.238 Hom.: 2610

Bravo AF: 0.180

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.7
DANN	Benign	0.65
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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: rs4853169; hg19: chr2-75906972; COSMIC: COSV58082482;