rs575841631

Variant names:

• chr19-5995607-C-G
• rs575841631
• NM_000635.4:c.2050G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-5995607-C-G
• chr19-5995607-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.36

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)

ACMG classification

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
RFX2	NM_000635.4	c.2050G>C	p.Asp684His	missense_variant	Exon 17 of 18	ENST00000303657.10	NP_000626.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RFX2	ENST00000303657.10	c.2050G>C	p.Asp684His	missense_variant	Exon 17 of 18	1	NM_000635.4	ENSP00000306335.4

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

Other links and lift over

dbSNP: rs575841631; hg19: chr19-5995618;