6-139372697-G-T

Variant names:

• chr6-139372697-G-T
• rs1131431
• NM_006079.5:c.*435C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006079.5(CITED2):​c.*435C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CITED2 NM_006079.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.96
• Publications: 0 publications found

Genes affected

CITED2 (HGNC:1987): (Cbp/p300 interacting transactivator with Glu/Asp rich carboxy-terminal domain 2) The protein encoded by this gene inhibits transactivation of HIF1A-induced genes by competing with binding of hypoxia-inducible factor 1-alpha to p300-CH1. Mutations in this gene are a cause of cardiac septal defects. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

CITED2 Gene-Disease associations (from GenCC):

• atrial septal defect 8

  Inheritance: AD Classification: MODERATE Submitted by: Laboratory for Molecular Medicine
• congenital heart defects, multiple types

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• ventricular septal defect 2

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000226571 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006079.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CITED2	NM_006079.5	MANE Select	c.*435C>A		3_prime_UTR	Exon 2 of 2	NP_006070.2
	CITED2	NM_001168389.3		c.*435C>A		3_prime_UTR	Exon 2 of 2	NP_001161861.2
	CITED2	NM_001168388.3		c.*435C>A		3_prime_UTR	Exon 2 of 2	NP_001161860.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CITED2	ENST00000367651.4	TSL:1 MANE Select	c.*435C>A		3_prime_UTR	Exon 2 of 2	ENSP00000356623.2
	CITED2	ENST00000537332.2	TSL:3	c.*435C>A		3_prime_UTR	Exon 2 of 2	ENSP00000444198.2
	CITED2	ENST00000536159.2	TSL:3	c.*435C>A		3_prime_UTR	Exon 2 of 2	ENSP00000442831.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 71296 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 38174

African (AFR) AF: 0.00 AC: 0 AN: 2460

American (AMR) AF: 0.00 AC: 0 AN: 4064

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1652

East Asian (EAS) AF: 0.00 AC: 0 AN: 4460

South Asian (SAS) AF: 0.00 AC: 0 AN: 11954

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3014

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 196

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 40166

Other (OTH) AF: 0.00 AC: 0 AN: 3330

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.84
PhyloP100		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1131431; hg19: chr6-139693834;