rs751501072

Variant names:

• chr6-139373365-CGCCGCT-C
• rs751501072
• NM_006079.5:c.574_579delAGCGGC

Your query was ambiguous. Multiple possible variants found:

• chr6-139373365-CGCCGCT-C
• chr6-139373365-CGCCGCT-CGCCGCTGCCGCT

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP3 BP6_Moderate BS2

The NM_006079.5(CITED2):​c.574_579delAGCGGC​(p.Ser192_Gly193del) variant causes a conservative 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (3 hom.)
• Consequence: CITED2 NM_006079.5 conservative_inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 4.53
• Publications: 2 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: Benign. The variant received -7 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_006079.5
• BP6: Variant 6-139373365-CGCCGCT-C is Benign according to our data. Variant chr6-139373365-CGCCGCT-C is described in ClinVar as Benign. ClinVar VariationId is 1684895.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 39 Unknown,AD gene.

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.574_579delAGCGGC	p.Ser192_Gly193del	conservative_inframe_deletion	Exon 2 of 2	NP_006070.2
	CITED2	NM_001168389.3		c.589_594delAGCGGC	p.Ser197_Gly198del	conservative_inframe_deletion	Exon 2 of 2	NP_001161861.2	A0A0A0MTM3
	CITED2	NM_001168388.3		c.574_579delAGCGGC	p.Ser192_Gly193del	conservative_inframe_deletion	Exon 2 of 2	NP_001161860.1	Q99967-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CITED2	ENST00000367651.4	TSL:1 MANE Select	c.574_579delAGCGGC	p.Ser192_Gly193del	conservative_inframe_deletion	Exon 2 of 2	ENSP00000356623.2	Q99967-1
	CITED2	ENST00000537332.2	TSL:3	c.589_594delAGCGGC	p.Ser197_Gly198del	conservative_inframe_deletion	Exon 2 of 2	ENSP00000444198.2	A0A0A0MTM3
	CITED2	ENST00000536159.2	TSL:3	c.574_579delAGCGGC	p.Ser192_Gly193del	conservative_inframe_deletion	Exon 2 of 2	ENSP00000442831.1	Q99967-1

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

GnomAD2 exomes AF: 0.000586 AC: 127 AN: 216568 AF XY: 0.000480

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 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

African (AFR) AF: 0.00 AC: 0 AN: 31672

American (AMR) AF: 0.0000467 AC: 2 AN: 42858

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25516

East Asian (EAS) AF: 0.00331 AC: 126 AN: 38034

South Asian (SAS) AF: 0.000178 AC: 15 AN: 84118

European-Finnish (FIN) AF: 0.0000203 AC: 1 AN: 49376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.0000657 AC: 72 AN: 1095586

Other (OTH) AF: 0.000357 AC: 21 AN: 58858

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

African (AFR) AF: 0.0000241 AC: 1 AN: 41482

American (AMR) AF: 0.000262 AC: 4 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00521 AC: 27 AN: 5180

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000444 AC: 3 AN: 67618

Other (OTH) AF: 0.000475 AC: 1 AN: 2104

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000246

Asia WGS AF: 0.00231 AC: 8 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	CITED2-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.5
Mutation Taster		=170/30	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs751501072; hg19: chr6-139694502;