rs2072446

chr17-49510457-C-Gchr17-49510457-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S205L) has been classified as Likely benign.

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

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NGFR	NM_002507.4	c.614C>G	p.Ser205Trp	missense_variant	4/6	ENST00000172229.8
NGFR-AS1	NR_103773.1	n.377+526G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NGFR	ENST00000172229.8	c.614C>G	p.Ser205Trp	missense_variant	4/6	1	NM_002507.4	P1
NGFR-AS1	ENST00000514506.1	n.377+526G>C		intron_variant, non_coding_transcript_variant		2
NGFR	ENST00000504201.1	c.332C>G	p.Ser111Trp	missense_variant	4/6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.076	D
MetaRNN	Benign	0.38	T;T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	1.9	L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.0	N;N
REVEL	Uncertain	0.31
Sift	Uncertain	0.015	D;D
Sift4G	Uncertain	0.028	D;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

Publications

LitVar

Other links and lift over

dbSNP: rs2072446; hg19: chr17-47587819;