ENST00000304053.11:c.*4748A>G

Variant names:

• chr9-84876565-A-G
• rs11140793
• ENST00000304053.11:c.*4748A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000304053.11(NTRK2):​c.*4748A>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 0.0000776 in 1,056,422 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000086 (0 hom.)
• Consequence: NTRK2 ENST00000304053.11 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117
• Publications: 12 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS2: High AC in GnomAdExome4 at 78 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000304053.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTRK2	NM_006180.6	MANE Select	c.1633+9134A>G		intron	N/A	NP_006171.2
	NTRK2	NM_001018065.2		c.*4748A>G		3_prime_UTR	Exon 15 of 15	NP_001018075.1
	NTRK2	NM_001369537.1		c.*4748A>G		3_prime_UTR	Exon 16 of 16	NP_001356466.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTRK2	ENST00000304053.11	TSL:1	c.*4748A>G		3_prime_UTR	Exon 13 of 13	ENSP00000306167.7
	NTRK2	ENST00000376208.6	TSL:1	c.*4748A>G		3_prime_UTR	Exon 16 of 16	ENSP00000365381.1
	NTRK2	ENST00000277120.8	TSL:1 MANE Select	c.1633+9134A>G		intron	N/A	ENSP00000277120.3

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000863 AC: 78 AN: 904276 Hom.: 0 Cov.: 31 AF XY: 0.000117 AC XY: 49 AN XY: 417642

African (AFR) AF: 0.0000522 AC: 1 AN: 19152

American (AMR) AF: 0.00 AC: 0 AN: 3158

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9704

East Asian (EAS) AF: 0.00 AC: 0 AN: 13726

South Asian (SAS) AF: 0.00 AC: 0 AN: 17078

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2060

European-Non Finnish (NFE) AF: 0.0000918 AC: 74 AN: 805818

Other (OTH) AF: 0.0000902 AC: 3 AN: 33254

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152146 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74344

African (AFR) AF: 0.00 AC: 0 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 850

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.82
DANN	Benign	0.53
PhyloP100		-0.12

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

Other links and lift over

dbSNP: rs11140793; hg19: chr9-87491480;