rs1624327

Variant names:

• chr9-84814375-A-G
• rs1624327
• ENST00000359847.4:c.*3796A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-84814375-A-G
• chr9-84814375-A-T

Variant summary

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

The ENST00000359847.4(NTRK2):​c.*3796A>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 0.713 in 1,065,262 control chromosomes in the GnomAD database, including 271,531 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 0.71 (38642 hom., cov: 33)
  • Exomes 𝑓: 0.71 (232889 hom.)
• Consequence: NTRK2 ENST00000359847.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230
• Publications: 17 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000359847.4. 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.1397-46665A>G		intron	N/A	NP_006171.2
	NTRK2	NM_001007097.3		c.*3796A>G		3_prime_UTR	Exon 15 of 15	NP_001007098.1
	NTRK2	NM_001369539.1		c.*3796A>G		3_prime_UTR	Exon 13 of 13	NP_001356468.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTRK2	ENST00000359847.4	TSL:1	c.*3796A>G		3_prime_UTR	Exon 14 of 14	ENSP00000352906.3
	NTRK2	ENST00000395882.6	TSL:1	c.*3796A>G		3_prime_UTR	Exon 15 of 15	ENSP00000379221.1
	NTRK2	ENST00000277120.8	TSL:1 MANE Select	c.1397-46665A>G		intron	N/A	ENSP00000277120.3

Frequencies

GnomAD3 genomes AF: 0.710 AC: 107980 AN: 152066 Hom.: 38609 Cov.: 33

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.865

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.703

GnomAD4 exome AF: 0.714 AC: 651669 AN: 913078 Hom.: 232889 Cov.: 43 AF XY: 0.714 AC XY: 300918 AN XY: 421494

African (AFR) AF: 0.635 AC: 12462 AN: 19624

American (AMR) AF: 0.717 AC: 2464 AN: 3438

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 6922 AN: 10206

East Asian (EAS) AF: 0.879 AC: 13109 AN: 14920

South Asian (SAS) AF: 0.799 AC: 13716 AN: 17158

European-Finnish (FIN) AF: 0.725 AC: 242 AN: 334

Middle Eastern (MID) AF: 0.742 AC: 1565 AN: 2108

European-Non Finnish (NFE) AF: 0.711 AC: 576805 AN: 811304

Other (OTH) AF: 0.717 AC: 24384 AN: 33986

GnomAD4 genome AF: 0.710 AC: 108067 AN: 152184 Hom.: 38642 Cov.: 33 AF XY: 0.715 AC XY: 53168 AN XY: 74398

African (AFR) AF: 0.643 AC: 26710 AN: 41512

American (AMR) AF: 0.719 AC: 10999 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 2411 AN: 3470

East Asian (EAS) AF: 0.865 AC: 4476 AN: 5174

South Asian (SAS) AF: 0.806 AC: 3889 AN: 4826

European-Finnish (FIN) AF: 0.745 AC: 7893 AN: 10592

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.725 AC: 49328 AN: 67992

Other (OTH) AF: 0.703 AC: 1488 AN: 2116

Alfa AF: 0.719 Hom.: 50694

Bravo AF: 0.702

Asia WGS AF: 0.782 AC: 2718 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.84
DANN	Benign	0.57
PhyloP100		-0.023
Mutation Taster		=100/0	polymorphism (auto)

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: rs1624327; hg19: chr9-87429290;