6-139373346-TTGCCGC-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4 BP6_Moderate BS2

The NM_006079.5(CITED2):c.593_598del(p.Ser198_Gly199del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000507 in 1,597,862 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (0 hom.)
• Consequence: CITED2 NM_006079.5 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter P:1 B:1
• Conservation: PhyloP100: 2.57

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 -4 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_006079.5.
• BP6: Variant 6-139373346-TTGCCGC-T is Benign according to our data. Variant chr6-139373346-TTGCCGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 6723.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-139373346-TTGCCGC-T is described in Lovd as [Likely_benign].
• BS2: High AC in GnomAd at 213 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CITED2	NM_006079.5	c.593_598del	p.Ser198_Gly199del	inframe_deletion	2/2	ENST00000367651.4
CITED2	NM_001168388.3	c.593_598del	p.Ser198_Gly199del	inframe_deletion	2/2
CITED2	NM_001168389.3	c.608_613del	p.Ser203_Gly204del	inframe_deletion	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CITED2	ENST00000367651.4	c.593_598del	p.Ser198_Gly199del	inframe_deletion	2/2	1	NM_006079.5	P1
	ENST00000650173.1	n.510-55722_510-55717del		intron_variant, non_coding_transcript_variant
CITED2	ENST00000536159.2	c.593_598del	p.Ser198_Gly199del	inframe_deletion	2/2	3		P1
CITED2	ENST00000537332.2	c.608_613del	p.Ser203_Gly204del	inframe_deletion	2/2	3

Frequencies

GnomAD3 genomes AF: 0.00140 AC: 213 AN: 152082 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00311

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00282

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.000407 AC: 90 AN: 221142 Hom.: 0 AF XY: 0.000381 AC XY: 47 AN XY: 123348

Gnomad AFR exome AF: 0.00350

Gnomad AMR exome AF: 0.000217

Gnomad ASJ exome AF: 0.000213

Gnomad EAS exome AF: 0.0000614

Gnomad SAS exome AF: 0.000206

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000278

Gnomad OTH exome AF: 0.00112

GnomAD4 exome AF: 0.000413 AC: 597 AN: 1445668 Hom.: 0 AF XY: 0.000412 AC XY: 296 AN XY: 719280

Gnomad4 AFR exome AF: 0.00289

Gnomad4 AMR exome AF: 0.000644

Gnomad4 ASJ exome AF: 0.000116

Gnomad4 EAS exome AF: 0.000182

Gnomad4 SAS exome AF: 0.000165

Gnomad4 FIN exome AF: 0.0000200

Gnomad4 NFE exome AF: 0.000357

Gnomad4 OTH exome AF: 0.000874

GnomAD4 genome AF: 0.00140 AC: 213 AN: 152194 Hom.: 1 Cov.: 32 AF XY: 0.00128 AC XY: 95 AN XY: 74426

Gnomad4 AFR AF: 0.00310

Gnomad4 AMR AF: 0.00281

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000500

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000291 Hom.: 0

Bravo AF: 0.00176

ClinVar

Significance: Likely benign

Submissions summary: Pathogenic:1 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Atrial septal defect 8 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 01, 2005

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

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: rs531316452; hg19: chr6-139694483;