Variant rs182932220 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005169.4(PHOX2A):c.156C>T(p.Leu52=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0311 in 1,261,934 control chromosomes in the GnomAD database, including 713 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 105 hom., cov: 32)

Exomes 𝑓: 0.032 ( 608 hom. )

Consequence

PHOX2A
NM_005169.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.25

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 11-72243849-G-A is Benign according to our data. Variant chr11-72243849-G-A is described in ClinVar as [Benign]. Clinvar id is 259655.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.25 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0262 (3990/152278) while in subpopulation NFE AF= 0.0346 (2350/68002). AF 95% confidence interval is 0.0334. There are 105 homozygotes in gnomad4. There are 2066 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 105 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHOX2A	NM_005169.4 linkuse as main transcript	c.156C>T	p.Leu52=	synonymous_variant	1/3	ENST00000298231.5	NP_005160.2
PHOX2A	XM_047426947.1 linkuse as main transcript	c.156C>T	p.Leu52=	synonymous_variant	1/3		XP_047282903.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHOX2A	ENST00000298231.5 linkuse as main transcript	c.156C>T	p.Leu52=	synonymous_variant	1/3	1	NM_005169.4	ENSP00000298231	P1
PHOX2A	ENST00000544057.1 linkuse as main transcript	n.85+1731C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0262

AC:

3988

AN:

152164

Hom.:

104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00620

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.0102

Gnomad ASJ

AF:

0.0498

Gnomad EAS

AF:

0.00909

Gnomad SAS

AF:

0.0165

Gnomad FIN

AF:

0.0790

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0346

Gnomad OTH

AF:

0.0206

GnomAD3 exomes

AF:

0.0517

AC:

471

AN:

9104

Hom.:

AF XY:

0.0549

AC XY:

268

AN XY:

4882

show subpopulations

Gnomad AFR exome

AF:

0.0171

Gnomad AMR exome

AF:

0.0143

Gnomad ASJ exome

AF:

0.0909

Gnomad EAS exome

AF:

0.0227

Gnomad SAS exome

AF:

0.0174

Gnomad FIN exome

AF:

0.0735

Gnomad NFE exome

AF:

0.0401

Gnomad OTH exome

AF:

0.0392

GnomAD4 exome

AF:

0.0318

AC:

35313

AN:

1109656

Hom.:

608

Cov.:

AF XY:

0.0315

AC XY:

16615

AN XY:

527938

show subpopulations

Gnomad4 AFR exome

AF:

0.00403

Gnomad4 AMR exome

AF:

0.0151

Gnomad4 ASJ exome

AF:

0.0384

Gnomad4 EAS exome

AF:

0.00364

Gnomad4 SAS exome

AF:

0.0173

Gnomad4 FIN exome

AF:

0.0701

Gnomad4 NFE exome

AF:

0.0329

Gnomad4 OTH exome

AF:

0.0262

GnomAD4 genome

AF:

0.0262

AC:

3990

AN:

152278

Hom.:

105

Cov.:

AF XY:

0.0278

AC XY:

2066

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00618

Gnomad4 AMR

AF:

0.0103

Gnomad4 ASJ

AF:

0.0498

Gnomad4 EAS

AF:

0.00912

Gnomad4 SAS

AF:

0.0163

Gnomad4 FIN

AF:

0.0790

Gnomad4 NFE

AF:

0.0346

Gnomad4 OTH

AF:

0.0213

Alfa

AF:

0.0361

Hom.:

Bravo

AF:

0.0202

Asia WGS

AF:

0.0120

AC:

AN:

3478

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

-0.50

CADD

Benign

DANN

Benign

0.92

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