rs2298948

chr2-75699439-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCFC2	NM_003203.5	c.717+1751A>G		intron_variant		ENST00000321027.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCFC2	ENST00000321027.8	c.717+1751A>G		intron_variant		1	NM_003203.5	P1

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

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.408

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.256

Alfa AF: 0.295 Hom.: 14395

Bravo AF: 0.240

Asia WGS AF: 0.287 AC: 994 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.6
Dann	Benign	0.69

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

Other links and lift over

dbSNP: rs2298948; hg19: chr2-75926565;