NM_006079.5:c.-9+77G>T

Variant names:

• chr6-139374336-C-A
• rs34394782
• NM_006079.5:c.-9+77G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006079.5(CITED2):​c.-9+77G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 488,206 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000020 (0 hom.)
• Consequence: CITED2 NM_006079.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.765
• Publications: 1 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
• congenital heart disease

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

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

ENSG00000226571 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CITED2	NM_006079.5	MANE Select	c.-9+77G>T		intron	N/A	NP_006070.2
	CITED2	NM_001168388.3		c.-81G>T		5_prime_UTR	Exon 1 of 2	NP_001161860.1	Q99967-1
	CITED2	NM_001168389.3		c.-198G>T		upstream_gene	N/A	NP_001161861.2	A0A0A0MTM3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CITED2	ENST00000367651.4	TSL:1 MANE Select	c.-9+77G>T		intron	N/A	ENSP00000356623.2	Q99967-1
	CITED2	ENST00000536159.2	TSL:3	c.-81G>T		5_prime_UTR	Exon 1 of 2	ENSP00000442831.1	Q99967-1
	CITED2	ENST00000935620.1		c.-9+77G>T		intron	N/A	ENSP00000605679.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 1 AN: 488206 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 248882

African (AFR) AF: 0.00 AC: 0 AN: 13396

American (AMR) AF: 0.00 AC: 0 AN: 14532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12576

East Asian (EAS) AF: 0.00 AC: 0 AN: 29232

South Asian (SAS) AF: 0.00 AC: 0 AN: 30372

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24738

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1982

European-Non Finnish (NFE) AF: 0.00000298 AC: 1 AN: 335046

Other (OTH) AF: 0.00 AC: 0 AN: 26332

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	19
DANN	Benign	0.94
PhyloP100		0.77
PromoterAI		0.029	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		3.0

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: rs34394782; hg19: chr6-139695473;