Genetic Variant CITED2:p.Ser198_Gly199del (chr6-139373346-TTGCCGC-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4BP6_ModerateBS2

The NM_006079.5(CITED2):c.593_598delGCGGCA(p.Ser198_Gly199del) variant causes a disruptive 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 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter P:1B:1

Conservation

PhyloP100: 2.57

Variant links:

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 links:

ENSG00000226571 (HGNC:):

ENSG00000226571 links:

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ACMG classification

Classification made for transcript

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 GnomAd4 at 213 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CITED2	NM_006079.5 link	c.593_598delGCGGCA	p.Ser198_Gly199del	disruptive_inframe_deletion	Exon 2 of 2	ENST00000367651.4	NP_006070.2	Q99967-1D9ZGF1
CITED2	NM_001168389.3 link	c.608_613delGCGGCA	p.Ser203_Gly204del	disruptive_inframe_deletion	Exon 2 of 2		NP_001161861.2	Q99967A0A0A0MTM3
CITED2	NM_001168388.3 link	c.593_598delGCGGCA	p.Ser198_Gly199del	disruptive_inframe_deletion	Exon 2 of 2		NP_001161860.1	Q99967-1D9ZGF1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CITED2	ENST00000367651.4 link	c.593_598delGCGGCA	p.Ser198_Gly199del	disruptive_inframe_deletion	Exon 2 of 2	1	NM_006079.5	ENSP00000356623.2	Q99967-1
CITED2	ENST00000537332.2 link	c.608_613delGCGGCA	p.Ser203_Gly204del	disruptive_inframe_deletion	Exon 2 of 2	3		ENSP00000444198.2	A0A0A0MTM3
CITED2	ENST00000536159.2 link	c.593_598delGCGGCA	p.Ser198_Gly199del	disruptive_inframe_deletion	Exon 2 of 2	3		ENSP00000442831.1	Q99967-1
ENSG00000226571	ENST00000650173.1 link	n.510-55722_510-55717delTGCCGC		intron_variant	Intron 4 of 7

Frequencies

GnomAD3 genomes

AF:

0.00140

AC:

213

AN:

152082

Hom.:

Cov.:

show subpopulations

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:

AN:

221142

Hom.:

AF XY:

0.000381

AC XY:

AN XY:

123348

show subpopulations

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.:

AF XY:

0.000412

AC XY:

296

AN XY:

719280

show subpopulations

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.:

Cov.:

AF XY:

0.00128

AC XY:

AN XY:

74426

show subpopulations

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.:

Bravo

AF:

0.00176

ClinVar

Significance: Likely benign

Submissions summary: Pathogenic:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Atrial septal defect 8

Pathogenic:1

Dec 01, 2005

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over