6-139373365-CGCCGCT-C

Position:

• chr6-139373365-CGCCGCT-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_006079.5(CITED2):​c.574_579del​(p.Ser192_Gly193del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000174 in 1,583,402 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (3 hom.)
• Consequence: CITED2 NM_006079.5 inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.53

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 Benign. Variant got -12 ACMG points.

• BP6: Variant 6-139373365-CGCCGCT-C is Benign according to our data. Variant chr6-139373365-CGCCGCT-C is described in ClinVar as [Likely_benign]. Clinvar id is 1684895.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 39 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CITED2	NM_006079.5	c.574_579del	p.Ser192_Gly193del	inframe_deletion	2/2	ENST00000367651.4
CITED2	NM_001168388.3	c.574_579del	p.Ser192_Gly193del	inframe_deletion	2/2
CITED2	NM_001168389.3	c.589_594del	p.Ser197_Gly198del	inframe_deletion	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CITED2	ENST00000367651.4	c.574_579del	p.Ser192_Gly193del	inframe_deletion	2/2	1	NM_006079.5	P1
	ENST00000650173.1	n.510-55714_510-55709del		intron_variant, non_coding_transcript_variant
CITED2	ENST00000536159.2	c.574_579del	p.Ser192_Gly193del	inframe_deletion	2/2	3		P1
CITED2	ENST00000537332.2	c.589_594del	p.Ser197_Gly198del	inframe_deletion	2/2	3

Frequencies

GnomAD3 genomes AF: 0.000257 AC: 39 AN: 151578 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000263

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00520

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000444

Gnomad OTH AF: 0.000480

GnomAD3 exomes AF: 0.000586 AC: 127 AN: 216568 Hom.: 1 AF XY: 0.000480 AC XY: 58 AN XY: 120856

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000632

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00756

Gnomad SAS exome AF: 0.000140

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000105

Gnomad OTH exome AF: 0.000193

GnomAD4 exome AF: 0.000166 AC: 237 AN: 1431714 Hom.: 3 AF XY: 0.000149 AC XY: 106 AN XY: 712600

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000467

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00331

Gnomad4 SAS exome AF: 0.000178

Gnomad4 FIN exome AF: 0.0000203

Gnomad4 NFE exome AF: 0.0000657

Gnomad4 OTH exome AF: 0.000357

GnomAD4 genome AF: 0.000257 AC: 39 AN: 151688 Hom.: 0 Cov.: 32 AF XY: 0.000337 AC XY: 25 AN XY: 74176

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00521

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000444

Gnomad4 OTH AF: 0.000475

Bravo AF: 0.000246

Asia WGS AF: 0.00231 AC: 8 AN: 3472

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

CITED2-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 09, 2019

This variant is classified as likely 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: rs751501072; hg19: chr6-139694502;