rs201396910

Variant names:

• chr12-111214281-C-A
• rs201396910
• NM_015267.4:c.145C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-111214281-C-A
• chr12-111214281-C-G
• chr12-111214281-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015267.4(CUX2):​c.145C>A​(p.Arg49Ser) 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. 12/21 in silico tools predict 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. R49C) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CUX2 NM_015267.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.38

Genes affected

CUX2 (HGNC:19347): (cut like homeobox 2) This gene encodes a protein which contains three CUT domains and a homeodomain; both domains are DNA-binding motifs. A similar gene, whose gene product possesses different DNA-binding activities, is located on chromosome on chromosome 7. Two pseudogenes of this gene have been identified on chromosomes 10 and 4. [provided by RefSeq, Jan 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06915316).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUX2	NM_015267.4	c.145C>A	p.Arg49Ser	missense_variant	Exon 2 of 22	ENST00000261726.11	NP_056082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUX2	ENST00000261726.11	c.145C>A	p.Arg49Ser	missense_variant	Exon 2 of 22	1	NM_015267.4	ENSP00000261726.6
CUX2	ENST00000397643.3	c.325C>A	p.Arg109Ser	missense_variant	Exon 3 of 8	1		ENSP00000380765.3
CUX2	ENST00000551604.2	n.-20C>A		upstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1455316 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 723970

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.049	T;.
Eigen	Benign	-0.18
Eigen_PC	Benign	0.097
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.069	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.95	N;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	0.58	N;N
REVEL	Benign	0.11
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0090	B;P
Vest4		0.28
MutPred		0.33		Gain of phosphorylation at R49 (P = 0.0166);.;
MVP		0.18
MPC		0.75
ClinPred		0.76	D
GERP RS		5.6
Varity_R		0.18
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs201396910; hg19: chr12-111652085;