Variant chr11-72244023-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005169.4(PHOX2A):c.-19G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0232 in 378,646 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 40 hom., cov: 30)

Exomes 𝑓: 0.025 ( 79 hom. )

Consequence

PHOX2A
NM_005169.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.62

Variant links:

Genes affected

PHOX2A (HGNC:691): (paired like homeobox 2A) The protein encoded by this gene contains a paired-like homeodomain most similar to that of the Drosophila aristaless gene product. The encoded protein plays a central role in development of the autonomic nervous system. It regulates the expression of tyrosine hydroxylase and dopamine beta-hydroxylase, two catecholaminergic biosynthetic enzymes essential for the differentiation and maintenance of the noradrenergic neurotransmitter phenotype. The encoded protein has also been shown to regulate transcription of the alpha3 nicotinic acetylcholine receptor gene. Mutations in this gene have been associated with autosomal recessive congenital fibrosis of the extraocular muscles. [provided by RefSeq, Jul 2008]

PHOX2A links:

PHOX2A (HGNC:):

PHOX2A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 11-72244023-C-T is Benign according to our data. Variant chr11-72244023-C-T is described in ClinVar as [Benign]. Clinvar id is 259654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHOX2A	NM_005169.4 linkuse as main transcript	c.-19G>A		5_prime_UTR_variant	1/3	ENST00000298231.5	NP_005160.2	O14813
PHOX2A	XM_047426947.1 linkuse as main transcript	c.-19G>A		5_prime_UTR_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHOX2A	ENST00000298231.5 linkuse as main transcript	c.-19G>A		5_prime_UTR_variant	1/3	1	NM_005169.4	ENSP00000298231.5		O14813
PHOX2A	ENST00000544057.1 linkuse as main transcript	n.85+1557G>A		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0197

AC:

2218

AN:

112726

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0197

Gnomad AMI

AF:

0.00868

Gnomad AMR

AF:

0.0397

Gnomad ASJ

AF:

0.0260

Gnomad EAS

AF:

0.106

Gnomad SAS

AF:

0.0623

Gnomad FIN

AF:

0.00413

Gnomad MID

AF:

0.0231

Gnomad NFE

AF:

0.00825

Gnomad OTH

AF:

0.0169

GnomAD3 exomes

AF:

0.0144

AC:

328

AN:

22810

Hom.:

AF XY:

0.0152

AC XY:

193

AN XY:

12716

show subpopulations

Gnomad AFR exome

AF:

0.0240

Gnomad AMR exome

AF:

0.0522

Gnomad ASJ exome

AF:

0.00990

Gnomad EAS exome

AF:

0.0726

Gnomad SAS exome

AF:

0.0476

Gnomad FIN exome

AF:

0.00511

Gnomad NFE exome

AF:

0.00604

Gnomad OTH exome

AF:

0.0153

GnomAD4 exome

AF:

0.0248

AC:

6586

AN:

265884

Hom.:

Cov.:

AF XY:

0.0252

AC XY:

3205

AN XY:

127272

show subpopulations

Gnomad4 AFR exome

AF:

0.0478

Gnomad4 AMR exome

AF:

0.118

Gnomad4 ASJ exome

AF:

0.0751

Gnomad4 EAS exome

AF:

0.193

Gnomad4 SAS exome

AF:

0.0846

Gnomad4 FIN exome

AF:

0.00763

Gnomad4 NFE exome

AF:

0.0150

Gnomad4 OTH exome

AF:

0.0461

GnomAD4 genome

AF:

0.0197

AC:

2217

AN:

112762

Hom.:

Cov.:

AF XY:

0.0213

AC XY:

1185

AN XY:

55600

show subpopulations

Gnomad4 AFR

AF:

0.0197

Gnomad4 AMR

AF:

0.0397

Gnomad4 ASJ

AF:

0.0260

Gnomad4 EAS

AF:

0.105

Gnomad4 SAS

AF:

0.0622

Gnomad4 FIN

AF:

0.00413

Gnomad4 NFE

AF:

0.00825

Gnomad4 OTH

AF:

0.0162

Alfa

AF:

0.00136

Hom.:

Bravo

AF:

0.0174

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.93

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