chr6-139373344-T-A

Variant names:

• chr6-139373344-T-A
• NM_006079.5:c.601A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006079.5(CITED2):​c.601A>T​(p.Met201Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CITED2 NM_006079.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.06
• Publications: 0 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
• ventricular septal defect 2

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000226571 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2031455).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CITED2	NM_006079.5	c.601A>T	p.Met201Leu	missense_variant	Exon 2 of 2	ENST00000367651.4	NP_006070.2
CITED2	NM_001168389.3	c.616A>T	p.Met206Leu	missense_variant	Exon 2 of 2		NP_001161861.2
CITED2	NM_001168388.3	c.601A>T	p.Met201Leu	missense_variant	Exon 2 of 2		NP_001161860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CITED2	ENST00000367651.4	c.601A>T	p.Met201Leu	missense_variant	Exon 2 of 2	1	NM_006079.5	ENSP00000356623.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Jun 10, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.601A>T (p.M201L) alteration is located in exon 2 (coding exon 1) of the CITED2 gene. This alteration results from a A to T substitution at nucleotide position 601, causing the methionine (M) at amino acid position 201 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Benign	0.91
DEOGEN2	Benign	0.12	T;T;T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.40	.;T;T
M_CAP	Benign	0.076	D
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;.;L
PhyloP100		2.1
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.54	N;.;N
REVEL	Benign	0.12
Sift	Benign	0.32	T;.;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.44
MutPred		0.54		Loss of catalytic residue at M201 (P = 0.0744);.;Loss of catalytic residue at M201 (P = 0.0744);
MVP		0.44
MPC		0.28
ClinPred		0.22	T
GERP RS		3.7
Varity_R		0.26
gMVP		0.21
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr6-139694481;