rs786200975

Positions:

• chr14-28767497-AGCCGCCGCC-A
• chr14-28767497-AGCCGCCGCC-AGCC
• chr14-28767497-AGCCGCCGCC-AGCCGCC
• chr14-28767497-AGCCGCCGCC-AGCCGCCGCCGCC
• chr14-28767497-AGCCGCCGCC-AGCCGCCGCCGCCGCC
• chr14-28767497-AGCCGCCGCC-AGCCGCCGCCGCCGCCGCC

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_005249.5(FOXG1):​c.228_236delGCCGCCGCC​(p.Pro77_Pro79del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000613 in 978,372 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000021 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: FOXG1 NM_005249.5 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.51

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:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 14-28767497-AGCCGCCGCC-A is Benign according to our data. Variant chr14-28767497-AGCCGCCGCC-A is described in ClinVar as [Likely_benign]. Clinvar id is 1094650.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXG1	NM_005249.5	c.228_236delGCCGCCGCC	p.Pro77_Pro79del	disruptive_inframe_deletion	1/1	ENST00000313071.7	NP_005240.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXG1	ENST00000313071.7	c.228_236delGCCGCCGCC	p.Pro77_Pro79del	disruptive_inframe_deletion	1/1	6	NM_005249.5	ENSP00000339004.3
FOXG1	ENST00000706482.1	c.228_236delGCCGCCGCC	p.Pro77_Pro79del	disruptive_inframe_deletion	2/2			ENSP00000516406.1
LINC01551	ENST00000675861.1	n.374+1494_374+1502delGCCGCCGCC		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0000214 AC: 3 AN: 139878 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000777

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000358 AC: 3 AN: 838494 Hom.: 0 AF XY: 0.00000251 AC XY: 1 AN XY: 398112

Gnomad4 AFR exome AF: 0.000192

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000214 AC: 3 AN: 139878 Hom.: 0 Cov.: 31 AF XY: 0.0000294 AC XY: 2 AN XY: 68002

Gnomad4 AFR AF: 0.0000777

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000340

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Rett syndrome, congenital variant Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 27, 2023

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs786200975; hg19: chr14-29236703;