Genetic Variant RFX2:p.Asp684His (chr19-5995607-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_000635.4(RFX2):c.2050G>C(p.Asp684His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D684N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

RFX2
NM_000635.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.36

Publications

1 publications found

Variant links:

Genes affected

RFX2 (HGNC:9983): (regulatory factor X2) This gene is a member of the regulatory factor X gene family, which encodes transcription factors that contain a highly-conserved winged helix DNA binding domain. The protein encoded by this gene is structurally related to regulatory factors X1, X3, X4, and X5. It is a transcriptional activator that can bind DNA as a monomer or as a heterodimer with other RFX family members. This protein can bind to cis elements in the promoter of the IL-5 receptor alpha gene. Two transcript variants encoding different isoforms have been described for this gene, and both variants utilize alternative polyadenylation sites. [provided by RefSeq, Jul 2008]

RFX2 links:

RANBP3-DT (HGNC:55312): (RANBP3 divergent transcript)

RANBP3-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.368227).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000635.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RFX2	NM_000635.4	MANE Select	c.2050G>C	p.Asp684His	missense	Exon 17 of 18	NP_000626.2
RFX2	NM_134433.3		c.1975G>C	p.Asp659His	missense	Exon 16 of 17	NP_602309.1	P48378-2
RANBP3-DT	NR_046376.1		n.113-16513C>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RFX2	ENST00000303657.10	TSL:1 MANE Select	c.2050G>C	p.Asp684His	missense	Exon 17 of 18	ENSP00000306335.4	P48378-1
RFX2	ENST00000359161.7	TSL:1	c.2050G>C	p.Asp684His	missense	Exon 17 of 18	ENSP00000352076.3	P48378-1
RFX2	ENST00000926861.1		c.2071G>C	p.Asp691His	missense	Exon 17 of 18	ENSP00000596920.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

157574

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

ExAC

AF:

0.0000104

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Uncertain

0.068

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.37

MetaSVM

Uncertain

0.0048

MutationAssessor

Uncertain

2.7

PhyloP100

4.4

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.5

REVEL

Uncertain

0.38

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.010

Polyphen

0.96

Vest4

0.40

MutPred

0.23

Gain of methylation at K685 (P = 0.045)

MVP

0.47

MPC

1.9

ClinPred

0.98

GERP RS

3.7

Varity_R

0.49

gMVP

0.45

Mutation Taster

=76/24

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over