Variant rs2278782 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000325.6(PITX2):c.411+166C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 713,554 control chromosomes in the GnomAD database, including 8,976 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.15 ( 1660 hom., cov: 34)

Exomes 𝑓: 0.16 ( 7316 hom. )

Consequence

PITX2
NM_000325.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.736

Variant links:

Genes affected

PITX2 (HGNC:9005): (paired like homeodomain 2) This gene encodes a member of the RIEG/PITX homeobox family, which is in the bicoid class of homeodomain proteins. The encoded protein acts as a transcription factor and regulates procollagen lysyl hydroxylase gene expression. This protein plays a role in the terminal differentiation of somatotroph and lactotroph cell phenotypes, is involved in the development of the eye, tooth and abdominal organs, and acts as a transcriptional regulator involved in basal and hormone-regulated activity of prolactin. Mutations in this gene are associated with Axenfeld-Rieger syndrome, iridogoniodysgenesis syndrome, and sporadic cases of Peters anomaly. A similar protein in other vertebrates is involved in the determination of left-right asymmetry during development. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

PITX2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_addAF=-0.764495).

BP6

Variant 4-110620998-G-A is Benign according to our data. Variant chr4-110620998-G-A is described in ClinVar as [Benign]. Clinvar id is 1238490.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PITX2	NM_000325.6 linkuse as main transcript	c.411+166C>T		intron_variant		ENST00000644743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PITX2	ENST00000644743.1 linkuse as main transcript	c.411+166C>T		intron_variant			NM_000325.6		Q99697-2

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22409

AN:

152210

Hom.:

1661

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.111

Gnomad AMR

AF:

0.148

Gnomad ASJ

AF:

0.154

Gnomad EAS

AF:

0.159

Gnomad SAS

AF:

0.187

Gnomad FIN

AF:

0.121

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.152

Gnomad OTH

AF:

0.154

GnomAD3 exomes

AF:

0.155

AC:

20896

AN:

135170

Hom.:

1728

AF XY:

0.158

AC XY:

11628

AN XY:

73546

show subpopulations

Gnomad AFR exome

AF:

0.136

Gnomad AMR exome

AF:

0.130

Gnomad ASJ exome

AF:

0.161

Gnomad EAS exome

AF:

0.152

Gnomad SAS exome

AF:

0.184

Gnomad FIN exome

AF:

0.119

Gnomad NFE exome

AF:

0.158

Gnomad OTH exome

AF:

0.166

GnomAD4 exome

AF:

0.157

AC:

88160

AN:

561226

Hom.:

7316

Cov.:

AF XY:

0.159

AC XY:

48208

AN XY:

303080

show subpopulations

Gnomad4 AFR exome

AF:

0.143

Gnomad4 AMR exome

AF:

0.130

Gnomad4 ASJ exome

AF:

0.156

Gnomad4 EAS exome

AF:

0.190

Gnomad4 SAS exome

AF:

0.185

Gnomad4 FIN exome

AF:

0.120

Gnomad4 NFE exome

AF:

0.155

Gnomad4 OTH exome

AF:

0.160

GnomAD4 genome

AF:

0.147

AC:

22411

AN:

152328

Hom.:

1660

Cov.:

AF XY:

0.147

AC XY:

10927

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.138

Gnomad4 AMR

AF:

0.148

Gnomad4 ASJ

AF:

0.154

Gnomad4 EAS

AF:

0.159

Gnomad4 SAS

AF:

0.187

Gnomad4 FIN

AF:

0.121

Gnomad4 NFE

AF:

0.152

Gnomad4 OTH

AF:

0.152

Alfa

AF:

0.155

Hom.:

1055

Bravo

AF:

0.147

TwinsUK

AF:

0.154

AC:

571

ALSPAC

AF:

0.143

AC:

553

ExAC

AF:

0.0804

AC:

3335

Asia WGS

AF:

0.202

AC:

701

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.89

FATHMM_MKL

Benign

0.64

MutationTaster

Benign

1.0

P;P;P;P;P

Vest4

0.23

GERP RS

2.7

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

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