14-28767485-C-CGCAGCAGCA

Variant names:

• chr14-28767485-C-CGCAGCAGCA
• rs398124201
• NM_005249.5:c.212_220dupAGCAGCAGC

Variant summary

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

The NM_005249.5(FOXG1):​c.212_220dupAGCAGCAGC​(p.Gln71_Gln73dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000219 in 911,162 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P74P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: FOXG1 NM_005249.5 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214
• Publications: 1 publications found

Genes affected

FOXG1 (HGNC:3811): (forkhead box G1) This locus encodes a member of the fork-head transcription factor family. The encoded protein, which functions as a transcriptional repressor, is highly expressed in neural tissues during brain development. Mutations at this locus have been associated with Rett syndrome and a diverse spectrum of neurodevelopmental disorders defined as part of the FOXG1 syndrome. This gene is disregulated in many types of cancer and is the target of multiple microRNAs that regulate the proliferation of tumor cells. [provided by RefSeq, Jul 2020]

LINC01551 (HGNC:19828): (long intergenic non-protein coding RNA 1551)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXG1	NM_005249.5	c.212_220dupAGCAGCAGC	p.Gln71_Gln73dup	disruptive_inframe_insertion	Exon 1 of 1	ENST00000313071.7	NP_005240.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXG1	ENST00000313071.7	c.212_220dupAGCAGCAGC	p.Gln71_Gln73dup	disruptive_inframe_insertion	Exon 1 of 1	6	NM_005249.5	ENSP00000339004.3
FOXG1	ENST00000706482.1	c.212_220dupAGCAGCAGC	p.Gln71_Gln73dup	disruptive_inframe_insertion	Exon 2 of 2			ENSP00000516406.1
LINC01551	ENST00000675861.1	n.374+1478_374+1486dupAGCAGCAGC		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000220 AC: 2 AN: 911162 Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0 AN XY: 440350

African (AFR) AF: 0.000110 AC: 2 AN: 18252

American (AMR) AF: 0.00 AC: 0 AN: 16728

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11830

East Asian (EAS) AF: 0.00 AC: 0 AN: 11312

South Asian (SAS) AF: 0.00 AC: 0 AN: 33370

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13704

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2174

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 771550

Other (OTH) AF: 0.00 AC: 0 AN: 32242

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.21

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs398124201; hg19: chr14-29236691;