6-139373359-TGCCGCC-T

Position:

• chr6-139373359-TGCCGCC-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_006079.5(CITED2):​c.580_585del​(p.Gly194_Gly195del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00252 in 1,591,230 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Benign (no stars). Synonymous variant affecting the same amino acid position (i.e. G194G) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (8 hom.)
• Consequence: CITED2 NM_006079.5 inframe_deletion
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.99

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]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 6-139373359-TGCCGCC-T is Benign according to our data. Variant chr6-139373359-TGCCGCC-T is described in ClinVar as [Benign]. Clinvar id is 3350409.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-139373359-TGCCGCC-T is described in Lovd as [Benign].
• BS2: High AC in GnomAd4 at 209 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CITED2	NM_006079.5	c.580_585del	p.Gly194_Gly195del	inframe_deletion	2/2	ENST00000367651.4	NP_006070.2
CITED2	NM_001168388.3	c.580_585del	p.Gly194_Gly195del	inframe_deletion	2/2		NP_001161860.1
CITED2	NM_001168389.3	c.595_600del	p.Gly199_Gly200del	inframe_deletion	2/2		NP_001161861.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CITED2	ENST00000367651.4	c.580_585del	p.Gly194_Gly195del	inframe_deletion	2/2	1	NM_006079.5	ENSP00000356623	P1
	ENST00000650173.1	n.510-55716_510-55711del		intron_variant, non_coding_transcript_variant
CITED2	ENST00000536159.2	c.580_585del	p.Gly194_Gly195del	inframe_deletion	2/2	3		ENSP00000442831	P1
CITED2	ENST00000537332.2	c.595_600del	p.Gly199_Gly200del	inframe_deletion	2/2	3		ENSP00000444198

Frequencies

GnomAD3 genomes AF: 0.00138 AC: 209 AN: 151932 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000721

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00252

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00127 AC: 271 AN: 213768 Hom.: 1 AF XY: 0.00125 AC XY: 150 AN XY: 119786

Gnomad AFR exome AF: 0.000644

Gnomad AMR exome AF: 0.000475

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000211

Gnomad NFE exome AF: 0.00247

Gnomad OTH exome AF: 0.00253

GnomAD4 exome AF: 0.00264 AC: 3793 AN: 1439190 Hom.: 8 AF XY: 0.00252 AC XY: 1804 AN XY: 716038

Gnomad4 AFR exome AF: 0.000377

Gnomad4 AMR exome AF: 0.000511

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000475

Gnomad4 FIN exome AF: 0.000288

Gnomad4 NFE exome AF: 0.00322

Gnomad4 OTH exome AF: 0.00317

GnomAD4 genome AF: 0.00137 AC: 209 AN: 152040 Hom.: 0 Cov.: 32 AF XY: 0.00135 AC XY: 100 AN XY: 74338

Gnomad4 AFR AF: 0.000482

Gnomad4 AMR AF: 0.000720

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.00252

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.000510 Hom.: 0

Bravo AF: 0.00156

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CITED2-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 26, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs752543125; hg19: chr6-139694496;