rs2072446

Variant names:

• chr17-49510457-C-G
• rs2072446
• NM_002507.4:c.614C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-49510457-C-G
• chr17-49510457-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002507.4(NGFR):​c.614C>G​(p.Ser205Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NGFR NM_002507.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72
• Publications: 70 publications found

Genes affected

NGFR (HGNC:7809): (nerve growth factor receptor) Nerve growth factor receptor contains an extracellular domain containing four 40-amino acid repeats with 6 cysteine residues at conserved positions followed by a serine/threonine-rich region, a single transmembrane domain, and a 155-amino acid cytoplasmic domain. The cysteine-rich region contains the nerve growth factor binding domain. [provided by RefSeq, Jul 2008]

NGFR-AS1 (HGNC:55555): (NGFR antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3785319).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002507.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGFR	NM_002507.4	MANE Select	c.614C>G	p.Ser205Trp	missense	Exon 4 of 6	NP_002498.1	P08138-1
	NGFR-AS1	NR_103773.1		n.377+526G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGFR	ENST00000172229.8	TSL:1 MANE Select	c.614C>G	p.Ser205Trp	missense	Exon 4 of 6	ENSP00000172229.3	P08138-1
	NGFR	ENST00000504201.1	TSL:2	c.332C>G	p.Ser111Trp	missense	Exon 4 of 6	ENSP00000421731.1	P08138-2
	NGFR-AS1	ENST00000514506.1	TSL:2	n.377+526G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.076	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.7
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.31
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.028	D
Polyphen		0.018	B
Vest4		0.55
MutPred		0.22		Loss of glycosylation at S205 (P = 0.0019)
MVP		0.80
MPC		1.2
ClinPred		0.69	D
GERP RS		4.7
Varity_R		0.088
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2072446; hg19: chr17-47587819;