chr9-84670804-G-T

Variant names:

• chr9-84670804-G-T
• rs200698390
• NM_006180.6:c.56G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006180.6(NTRK2):​c.56G>T​(p.Cys19Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,730 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: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: NTRK2 NM_006180.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.40

Genes affected

NTRK2 (HGNC:8032): (neurotrophic receptor tyrosine kinase 2) This gene encodes a member of the neurotrophic tyrosine receptor kinase (NTRK) family. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. Signalling through this kinase leads to cell differentiation. Mutations in this gene have been associated with obesity and mood disorders. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.56G>T	p.Cys19Phe	missense_variant	Exon 2 of 19	ENST00000277120.8	NP_006171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTRK2	ENST00000277120.8	c.56G>T	p.Cys19Phe	missense_variant	Exon 2 of 19	1	NM_006180.6	ENSP00000277120.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251242 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135822

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461730 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727166

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Pathogenic	0.18
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Uncertain	0.47	.;T;.;.;.;.;T;.
Eigen	Benign	0.0054
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.83	T;T;T;T;T;.;.;.
M_CAP	Benign	0.063	D
MetaRNN	Uncertain	0.46	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.97	L;L;L;L;L;L;L;L
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.4	N;N;D;D;D;N;N;D
REVEL	Uncertain	0.38
Sift	Benign	0.14	T;T;T;T;T;T;T;T
Sift4G	Benign	0.44	T;T;T;T;T;T;T;T
Polyphen		0.034	B;B;B;B;B;B;B;B
Vest4		0.80
MutPred		0.37		Gain of MoRF binding (P = 0.1013);Gain of MoRF binding (P = 0.1013);Gain of MoRF binding (P = 0.1013);Gain of MoRF binding (P = 0.1013);Gain of MoRF binding (P = 0.1013);Gain of MoRF binding (P = 0.1013);Gain of MoRF binding (P = 0.1013);Gain of MoRF binding (P = 0.1013);
MVP		0.85
MPC		1.9
ClinPred		0.66	D
GERP RS		5.0
Varity_R		0.47
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs200698390; hg19: chr9-87285719;