9-85025721-A-G

Variant names:

• chr9-85025721-A-G
• rs1387923
• NM_006180.6:c.*4284A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006180.6(NTRK2):​c.*4284A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 232,770 control chromosomes in the GnomAD database, including 28,159 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.47 (17559 hom., cov: 32)
  • Exomes 𝑓: 0.50 (10600 hom.)
• Consequence: NTRK2 NM_006180.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.519
• Publications: 22 publications found

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]

NTRK2 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 58

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• obesity, hyperphagia, and developmental delay

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• infantile spasms

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.*4284A>G		3_prime_UTR_variant	Exon 19 of 19	ENST00000277120.8	NP_006171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTRK2	ENST00000277120.8	c.*4284A>G		3_prime_UTR_variant	Exon 19 of 19	1	NM_006180.6	ENSP00000277120.3

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71383 AN: 151818 Hom.: 17556 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.497

GnomAD4 exome AF: 0.496 AC: 40092 AN: 80834 Hom.: 10600 Cov.: 0 AF XY: 0.499 AC XY: 18523 AN XY: 37148

African (AFR) AF: 0.349 AC: 1360 AN: 3896

American (AMR) AF: 0.447 AC: 1117 AN: 2498

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 2872 AN: 5110

East Asian (EAS) AF: 0.188 AC: 2138 AN: 11378

South Asian (SAS) AF: 0.516 AC: 362 AN: 702

European-Finnish (FIN) AF: 0.483 AC: 28 AN: 58

Middle Eastern (MID) AF: 0.612 AC: 301 AN: 492

European-Non Finnish (NFE) AF: 0.567 AC: 28328 AN: 49936

Other (OTH) AF: 0.530 AC: 3586 AN: 6764

GnomAD4 genome AF: 0.470 AC: 71410 AN: 151936 Hom.: 17559 Cov.: 32 AF XY: 0.464 AC XY: 34468 AN XY: 74246

African (AFR) AF: 0.347 AC: 14408 AN: 41468

American (AMR) AF: 0.435 AC: 6635 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1936 AN: 3472

East Asian (EAS) AF: 0.265 AC: 1372 AN: 5170

South Asian (SAS) AF: 0.527 AC: 2538 AN: 4818

European-Finnish (FIN) AF: 0.496 AC: 5215 AN: 10506

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.556 AC: 37739 AN: 67936

Other (OTH) AF: 0.497 AC: 1046 AN: 2106

Alfa AF: 0.509 Hom.: 34289

Bravo AF: 0.458

Asia WGS AF: 0.461 AC: 1606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.61
DANN	Benign	0.43
PhyloP100		-0.52

Splicing

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

Other links and lift over

dbSNP: rs1387923; hg19: chr9-87640636;