rs575841631

Variant summary

Our verdict is Uncertain significance. Variant got 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

1
13
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.36
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]
RANBP3-DT (HGNC:55312): (RANBP3 divergent transcript)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.368227).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RFX2NM_000635.4 linkc.2050G>C p.Asp684His missense_variant Exon 17 of 18 ENST00000303657.10 NP_000626.2 P48378-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RFX2ENST00000303657.10 linkc.2050G>C p.Asp684His missense_variant Exon 17 of 18 1 NM_000635.4 ENSP00000306335.4 P48378-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000508
Hom.:
0
ExAC
AF:
0.0000104
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.27
BayesDel_addAF
Uncertain
0.068
T
BayesDel_noAF
Benign
-0.14
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.35
T;T;.
Eigen
Uncertain
0.35
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.90
.;D;D
M_CAP
Uncertain
0.17
D
MetaRNN
Benign
0.37
T;T;T
MetaSVM
Uncertain
0.0048
D
MutationAssessor
Uncertain
2.7
M;M;.
PrimateAI
Uncertain
0.61
T
PROVEAN
Uncertain
-3.5
D;.;.
REVEL
Uncertain
0.38
Sift
Uncertain
0.0020
D;.;.
Sift4G
Uncertain
0.010
D;D;D
Polyphen
0.96
D;D;D
Vest4
0.40
MutPred
0.23
Gain of methylation at K685 (P = 0.045);Gain of methylation at K685 (P = 0.045);.;
MVP
0.47
MPC
1.9
ClinPred
0.98
D
GERP RS
3.7
Varity_R
0.49
gMVP
0.45

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

LitVar

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

Other links and lift over

dbSNP: rs575841631; hg19: chr19-5995618; API