2-75699439-T-C

Variant names:

• chr2-75699439-T-C
• rs2298948
• NM_003203.5:c.717+1751A>G

Variant summary

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

The NM_003203.5(GCFC2):​c.717+1751A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,120 control chromosomes in the GnomAD database, including 5,268 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 0.25 (5268 hom., cov: 32)
• Consequence: GCFC2 NM_003203.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.712
• Publications: 22 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCFC2	NM_003203.5	MANE Select	c.717+1751A>G		intron	N/A	NP_003194.3
	GCFC2	NM_001410845.1		c.603+1751A>G		intron	N/A	NP_001397774.1
	GCFC2	NM_001201334.2		c.210+1751A>G		intron	N/A	NP_001188263.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCFC2	ENST00000321027.8	TSL:1 MANE Select	c.717+1751A>G		intron	N/A	ENSP00000318690.3
	GCFC2	ENST00000470197.5	TSL:1	n.183+1751A>G		intron	N/A
	GCFC2	ENST00000884726.1		c.741+1751A>G		intron	N/A	ENSP00000554785.1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37521 AN: 152002 Hom.: 5270 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.259

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.247 AC: 37514 AN: 152120 Hom.: 5268 Cov.: 32 AF XY: 0.250 AC XY: 18569 AN XY: 74356

African (AFR) AF: 0.109 AC: 4539 AN: 41518

American (AMR) AF: 0.271 AC: 4144 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1416 AN: 3468

East Asian (EAS) AF: 0.405 AC: 2095 AN: 5170

South Asian (SAS) AF: 0.290 AC: 1400 AN: 4824

European-Finnish (FIN) AF: 0.256 AC: 2702 AN: 10566

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20375 AN: 67984

Other (OTH) AF: 0.256 AC: 538 AN: 2104

Alfa AF: 0.286 Hom.: 27883

Bravo AF: 0.240

Asia WGS AF: 0.287 AC: 994 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.69
PhyloP100		-0.71
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: rs2298948; hg19: chr2-75926565;