Variant 11-72240115-GGCGCCCGCCGCGCCCGCC-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4

The NM_005169.4(PHOX2A):c.471_488delGGCGGGCGCGGCGGGCGC(p.Ala158_Ala163del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000000725 in 1,379,908 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: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

PHOX2A
NM_005169.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.56

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_005169.4.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHOX2A	NM_005169.4 link	c.471_488delGGCGGGCGCGGCGGGCGC	p.Ala158_Ala163del	disruptive_inframe_deletion	Exon 3 of 3	ENST00000298231.5	NP_005160.2	O14813
PHOX2A	NM_001425096.1 link	c.555_572delGGCGGGCGCGGCGGGCGC	p.Ala186_Ala191del	disruptive_inframe_deletion	Exon 3 of 3		NP_001412025.1
PHOX2A	NM_001425097.1 link	c.495_512delGGCGGGCGCGGCGGGCGC	p.Ala166_Ala171del	disruptive_inframe_deletion	Exon 3 of 3		NP_001412026.1
PHOX2A	NM_001425098.1 link	c.350_367delGGCGGGCGCGGCGGGCGC		3_prime_UTR_variant	Exon 3 of 3		NP_001412027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PHOX2A	ENST00000298231.5 link	c.471_488delGGCGGGCGCGGCGGGCGC	p.Ala158_Ala163del	disruptive_inframe_deletion	Exon 3 of 3	1	NM_005169.4	ENSP00000298231.5	O14813
PHOX2A	ENST00000546310.1 link	c.85-214_85-197delGGCGGGCGCGGCGGGCGC		intron_variant	Intron 1 of 1	5		ENSP00000444845.1	H0YGU5
PHOX2A	ENST00000544057.1 link	n.339_356delGGCGGGCGCGGCGGGCGC		non_coding_transcript_exon_variant	Exon 3 of 3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.25e-7

AC:

AN:

1379908

Hom.:

AF XY:

0.00000147

AC XY:

AN XY:

680768

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.29e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over