Genetic Variant CITED2:p.Gly195dup (chr6-139373359-T-TGCC) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3BS2

The NM_006079.5(CITED2):c.583_585dupGGC(p.Gly195dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000214 in 1,591,122 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

CITED2
NM_006079.5 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.99

Publications

0 publications found

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 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)

CITED2 links:

ENSG00000226571 (HGNC:):

ENSG00000226571 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_006079.5

BS2

High AC in GnomAdExome4 at 32 AD,Unknown 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CITED2	NM_006079.5	MANE Select	c.583_585dupGGC	p.Gly195dup	conservative_inframe_insertion	Exon 2 of 2	NP_006070.2
CITED2	NM_001168389.3		c.598_600dupGGC	p.Gly200dup	conservative_inframe_insertion	Exon 2 of 2	NP_001161861.2	A0A0A0MTM3
CITED2	NM_001168388.3		c.583_585dupGGC	p.Gly195dup	conservative_inframe_insertion	Exon 2 of 2	NP_001161860.1	Q99967-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CITED2	ENST00000367651.4	TSL:1 MANE Select	c.583_585dupGGC	p.Gly195dup	conservative_inframe_insertion	Exon 2 of 2	ENSP00000356623.2	Q99967-1
CITED2	ENST00000537332.2	TSL:3	c.598_600dupGGC	p.Gly200dup	conservative_inframe_insertion	Exon 2 of 2	ENSP00000444198.2	A0A0A0MTM3
CITED2	ENST00000536159.2	TSL:3	c.583_585dupGGC	p.Gly195dup	conservative_inframe_insertion	Exon 2 of 2	ENSP00000442831.1	Q99967-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151932

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000468

AC:

AN:

213768

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000107

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000222

AC:

AN:

1439190

Hom.:

Cov.:

AF XY:

0.0000154

AC XY:

AN XY:

716038

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31790

American (AMR)

AF:

0.00

AC:

AN:

43022

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25584

East Asian (EAS)

AF:

0.0000262

AC:

AN:

38144

South Asian (SAS)

AF:

0.00

AC:

AN:

84260

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5710

European-Non Finnish (NFE)

AF:

0.0000263

AC:

AN:

1102812

Other (OTH)

AF:

0.0000338

AC:

AN:

59238

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151932

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74220

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41372

American (AMR)

AF:

0.00

AC:

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67918

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.0

Mutation Taster

=80/20

polymorphism

(source)

Splicing

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

Publications

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6-139373359-TGCCGCC-TGCCGCCGCC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over