12-111214190-A-T

Position:

• chr12-111214190-A-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_015267.4(CUX2):​c.64-10A>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (0 hom., cov: 21)
  • Exomes 𝑓: 0.024 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CUX2 NM_015267.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0009105
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.82

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 12-111214190-A-T is Benign according to our data. Variant chr12-111214190-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 771184.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUX2	NM_015267.4	c.64-10A>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000261726.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUX2	ENST00000261726.11	c.64-10A>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_015267.4	P1
CUX2	ENST00000397643.3	c.244-10A>T		splice_polypyrimidine_tract_variant, intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1862 AN: 68662 Hom.: 0 Cov.: 21 FAILED QC

Gnomad AFR AF: 0.0455

Gnomad AMI AF: 0.00940

Gnomad AMR AF: 0.0148

Gnomad ASJ AF: 0.0166

Gnomad EAS AF: 0.0178

Gnomad SAS AF: 0.0320

Gnomad FIN AF: 0.0303

Gnomad MID AF: 0.0170

Gnomad NFE AF: 0.0220

Gnomad OTH AF: 0.0244

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0243 AC: 18853 AN: 774860 Hom.: 0 Cov.: 16 AF XY: 0.0286 AC XY: 10842 AN XY: 379244

Gnomad4 AFR exome AF: 0.0308

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.0370

Gnomad4 EAS exome AF: 0.0422

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.120

Gnomad4 NFE exome AF: 0.0121

Gnomad4 OTH exome AF: 0.0187

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0272 AC: 1866 AN: 68652 Hom.: 0 Cov.: 21 AF XY: 0.0257 AC XY: 876 AN XY: 34108

Gnomad4 AFR AF: 0.0456

Gnomad4 AMR AF: 0.0149

Gnomad4 ASJ AF: 0.0166

Gnomad4 EAS AF: 0.0175

Gnomad4 SAS AF: 0.0319

Gnomad4 FIN AF: 0.0303

Gnomad4 NFE AF: 0.0220

Gnomad4 OTH AF: 0.0253

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

Aug 04, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	14
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00091
dbscSNV1_RF	Benign	0.14
SpliceAI score (max)		0.10		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: rs201254067; hg19: chr12-111651994; COSMIC: COSV55649920; COSMIC: COSV55649920;