Variant 4-41745990-TGCCGCCGCCGCCGCTGCCGCGGCCGCC-TGCC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP5BS2

The NM_003924.4(PHOX2B):c.738_761del(p.Ala253_Ala260del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000147 in 1,089,222 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in Lovd as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. A246A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000015 ( 1 hom. )

Consequence

PHOX2B
NM_003924.4 inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.12

Variant links:

Genes affected

PHOX2B (HGNC:9143): (paired like homeobox 2B) The DNA-associated protein encoded by this gene is a member of the paired family of homeobox proteins localized to the nucleus. The protein functions as a transcription factor involved in the development of several major noradrenergic neuron populations and the determination of neurotransmitter phenotype. The gene product is linked to enhancement of second messenger-mediated activation of the dopamine beta-hydroylase, c-fos promoters and several enhancers, including cyclic amp-response element and serum-response element. Expansion of a 20 amino acid polyalanine tract in this protein by 5-13 aa has been associated with congenital central hypoventilation syndrome. [provided by RefSeq, Jul 2016]

PHOX2B links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP5

Variant 4-41745990-TGCCGCCGCCGCCGCTGCCGCGGCC-T is Pathogenic according to our data. Variant chr4-41745990-TGCCGCCGCCGCCGCTGCCGCGGCC-T is described in Lovd as [Pathogenic].

BS2

High AC in GnomAdExome4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHOX2B	NM_003924.4 linkuse as main transcript	c.738_761del	p.Ala253_Ala260del	inframe_deletion	3/3	ENST00000226382.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHOX2B	ENST00000226382.4 linkuse as main transcript	c.738_761del	p.Ala253_Ala260del	inframe_deletion	3/3	1	NM_003924.4	P1
PHOX2B	ENST00000510424.2 linkuse as main transcript			downstream_gene_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000147

AC:

AN:

1089222

Hom.:

AF XY:

0.0000153

AC XY:

AN XY:

522656

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:

0.0000855

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000151

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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