chr22-35744211-G-C

Position:

• chr22-35744211-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001394114.1(RBFOX2):​c.1298C>G​(p.Pro433Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBFOX2 NM_001394114.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.15

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09619185).
• BP6: Variant 22-35744211-G-C is Benign according to our data. Variant chr22-35744211-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2857566.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBFOX2	NM_001349999.2	c.1338C>G	p.Pro446Pro	synonymous_variant	14/14	ENST00000695854.1	NP_001336928.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBFOX2	ENST00000414461.6	c.1097C>G	p.Pro366Arg	missense_variant	12/12	1		ENSP00000407855.2
RBFOX2	ENST00000695854.1	c.1338C>G	p.Pro446Pro	synonymous_variant	14/14		NM_001349999.2	ENSP00000512219.1
RBFOX2	ENST00000438146.7	c.1350C>G	p.Pro450Pro	synonymous_variant	14/14	1		ENSP00000413035.2
RBFOX2	ENST00000449924.6	c.1137C>G	p.Pro379Pro	synonymous_variant	13/13	1		ENSP00000391670.2
RBFOX2	ENST00000695805.1	n.*631C>G		non_coding_transcript_exon_variant	13/13			ENSP00000512185.1
RBFOX2	ENST00000695805.1	n.*631C>G		3_prime_UTR_variant	13/13			ENSP00000512185.1
RBFOX2	ENST00000695807.1	n.*4321C>G		downstream_gene_variant				ENSP00000512187.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 19, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	12
DANN	Uncertain	1.0
Eigen	Benign	-0.091
Eigen_PC	Benign	0.060
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.096	T;T;T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-0.78	N;N;N
REVEL	Benign	0.094
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.0	B;B;B
Vest4		0.32
MutPred		0.25		.;Loss of catalytic residue at P365 (P = 0.016);Loss of catalytic residue at P365 (P = 0.016);
MVP		0.27
ClinPred		0.85	D
GERP RS		3.9

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-36140258;