Genetic Variant RBFOX2:p.Ala403_Ala405dup (chr22-35746483-A-AAGCGGCTGC) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM4BS2

The NM_001349999.2(RBFOX2):c.1207_1215dupGCAGCCGCT(p.Ala403_Ala405dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000965 in 1,450,892 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

RBFOX2
NM_001349999.2 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.40

Variant links:

Genes affected

RBFOX2 (HGNC:9906): (RNA binding fox-1 homolog 2) This gene is one of several human genes similar to the C. elegans gene Fox-1. This gene encodes an RNA binding protein that is thought to be a key regulator of alternative exon splicing in the nervous system and other cell types. The protein binds to a conserved UGCAUG element found downstream of many alternatively spliced exons and promotes inclusion of the alternative exon in mature transcripts. The protein also interacts with the estrogen receptor 1 transcription factor and regulates estrogen receptor 1 transcriptional activity. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

RBFOX2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001349999.2.

BS2

High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX2	NM_001349999.2 link	c.1207_1215dupGCAGCCGCT	p.Ala403_Ala405dup	conservative_inframe_insertion	Exon 12 of 14	ENST00000695854.1	NP_001336928.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RBFOX2	ENST00000695854.1 link	c.1207_1215dupGCAGCCGCT	p.Ala403_Ala405dup	conservative_inframe_insertion	Exon 12 of 14		NM_001349999.2	ENSP00000512219.1	A0A8Q3WKT3
RBFOX2	ENST00000438146.7 link	c.1219_1227dupGCAGCCGCT	p.Ala407_Ala409dup	conservative_inframe_insertion	Exon 12 of 14	1		ENSP00000413035.2	O43251-8
RBFOX2	ENST00000449924.6 link	c.1006_1014dupGCAGCCGCT	p.Ala336_Ala338dup	conservative_inframe_insertion	Exon 11 of 13	1		ENSP00000391670.2	O43251-10
RBFOX2	ENST00000414461.6 link	c.966_974dupGCAGCCGCT	p.Leu325_Thr326insGlnProLeu	disruptive_inframe_insertion	Exon 10 of 12	1		ENSP00000407855.2	O43251-4
RBFOX2	ENST00000695805.1 link	n.500_508dupGCAGCCGCT		non_coding_transcript_exon_variant	Exon 11 of 13			ENSP00000512185.1	A0A8Q3SI20
RBFOX2	ENST00000695807.1 link	n.4190_4198dupGCAGCCGCT		non_coding_transcript_exon_variant	Exon 13 of 15			ENSP00000512187.1	A0A8Q3SI31
RBFOX2	ENST00000695805.1 link	n.500_508dupGCAGCCGCT		3_prime_UTR_variant	Exon 11 of 13			ENSP00000512185.1	A0A8Q3SI20
RBFOX2	ENST00000695807.1 link	n.4190_4198dupGCAGCCGCT		3_prime_UTR_variant	Exon 13 of 15			ENSP00000512187.1	A0A8Q3SI31

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000124

AC:

AN:

242488

Hom.:

AF XY:

0.0000152

AC XY:

AN XY:

131460

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000300

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.00000922

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000965

AC:

AN:

1450892

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

722142

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000230

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.00000996

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

22-35746483-AAGCGGCTGC-AAGCGGCTGCAGCGGCTGC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over