chr1-115286114-CCG-T

Variant names:

• chr1-115286114-CCG-T
• NM_002506.3:c.680_682delCGGinsA

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Moderate PM2 PP5_Moderate

The NM_002506.3(NGF):​c.680_682delCGGinsA​(p.Thr227AsnfsTer44) variant causes a frameshift, missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. T227T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NGF NM_002506.3 frameshift, missense
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 6.80

Genes affected

NGF (HGNC:7808): (nerve growth factor) This gene is a member of the NGF-beta family and encodes a secreted protein which homodimerizes and is incorporated into a larger complex. This protein has nerve growth stimulating activity and the complex is involved in the regulation of growth and the differentiation of sympathetic and certain sensory neurons. Mutations in this gene have been associated with hereditary sensory and autonomic neuropathy, type 5 (HSAN5), and dysregulation of this gene's expression is associated with allergic rhinitis. [provided by RefSeq, Jul 2008]

NGF-AS1 (HGNC:53922): (NGF antisense RNA 1)

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0634 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-115286114-CCG-T is Pathogenic according to our data. Variant chr1-115286114-CCG-T is described in ClinVar as [Pathogenic]. Clinvar id is 29802.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NGF	NM_002506.3	c.680_682delCGGinsA	p.Thr227AsnfsTer44	frameshift_variant, missense_variant	Exon 3 of 3	ENST00000369512.3	NP_002497.2
NGF	XM_011541518.3	c.845_847delCGGinsA	p.Thr282AsnfsTer44	frameshift_variant, missense_variant	Exon 3 of 3		XP_011539820.1
NGF	XM_006710663.4	c.680_682delCGGinsA	p.Thr227AsnfsTer44	frameshift_variant, missense_variant	Exon 2 of 2		XP_006710726.1
NGF-AS1	NR_157569.1	n.207+2874_207+2876delCCGinsT		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NGF	ENST00000369512.3	c.680_682delCGGinsA	p.Thr227AsnfsTer44	frameshift_variant, missense_variant	Exon 3 of 3	1	NM_002506.3	ENSP00000358525.2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Peripheral neuropathy Pathogenic:1

Oct 04, 2024

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

PVS1,PS3,PP1,PM2 -

Congenital sensory neuropathy with selective loss of small myelinated fibers Pathogenic:1

Oct 31, 2014

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-115828735;