rs2472737

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020975.6(RET):c.2608-24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,611,680 control chromosomes in the GnomAD database, including 39,224 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3284 hom., cov: 33)

Exomes 𝑓: 0.22 ( 35940 hom. )

Consequence

RET
NM_020975.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.305

Variant links:

Genes affected

RET (HGNC:9967): (ret proto-oncogene) This gene encodes a transmembrane receptor and member of the tyrosine protein kinase family of proteins. Binding of ligands such as GDNF (glial cell-line derived neurotrophic factor) and other related proteins to the encoded receptor stimulates receptor dimerization and activation of downstream signaling pathways that play a role in cell differentiation, growth, migration and survival. The encoded receptor is important in development of the nervous system, and the development of organs and tissues derived from the neural crest. This proto-oncogene can undergo oncogenic activation through both cytogenetic rearrangement and activating point mutations. Mutations in this gene are associated with Hirschsprung disease and central hypoventilation syndrome and have been identified in patients with renal agenesis. [provided by RefSeq, Sep 2017]

RET links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 10-43120057-G-A is Benign according to our data. Variant chr10-43120057-G-A is described in ClinVar as [Benign]. Clinvar id is 24956.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-43120057-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RET	NM_020975.6 link	c.2608-24G>A		intron_variant	Intron 14 of 19	ENST00000355710.8	NP_066124.1	P07949-1A0A024R7T2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RET	ENST00000355710.8 link	c.2608-24G>A		intron_variant	Intron 14 of 19	5	NM_020975.6	ENSP00000347942.3		P07949-1

Frequencies

GnomAD3 genomes

AF:

0.202

AC:

30780

AN:

152050

Hom.:

3272

Cov.:

show subpopulations

Gnomad AFR

AF:

0.150

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.231

Gnomad SAS

AF:

0.158

Gnomad FIN

AF:

0.293

Gnomad MID

AF:

0.185

Gnomad NFE

AF:

0.227

Gnomad OTH

AF:

0.192

GnomAD3 exomes

AF:

0.204

AC:

50418

AN:

247006

Hom.:

5325

AF XY:

0.204

AC XY:

27337

AN XY:

133778

show subpopulations

Gnomad AFR exome

AF:

0.150

Gnomad AMR exome

AF:

0.153

Gnomad ASJ exome

AF:

0.124

Gnomad EAS exome

AF:

0.233

Gnomad SAS exome

AF:

0.160

Gnomad FIN exome

AF:

0.289

Gnomad NFE exome

AF:

0.226

Gnomad OTH exome

AF:

0.197

GnomAD4 exome

AF:

0.219

AC:

319375

AN:

1459512

Hom.:

35940

Cov.:

AF XY:

0.217

AC XY:

157520

AN XY:

725856

show subpopulations

Gnomad4 AFR exome

AF:

0.141

Gnomad4 AMR exome

AF:

0.156

Gnomad4 ASJ exome

AF:

0.121

Gnomad4 EAS exome

AF:

0.215

Gnomad4 SAS exome

AF:

0.162

Gnomad4 FIN exome

AF:

0.278

Gnomad4 NFE exome

AF:

0.228

Gnomad4 OTH exome

AF:

0.208

GnomAD4 genome

AF:

0.203

AC:

30818

AN:

152168

Hom.:

3284

Cov.:

AF XY:

0.206

AC XY:

15282

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.150

Gnomad4 AMR

AF:

0.193

Gnomad4 ASJ

AF:

0.121

Gnomad4 EAS

AF:

0.231

Gnomad4 SAS

AF:

0.158

Gnomad4 FIN

AF:

0.293

Gnomad4 NFE

AF:

0.227

Gnomad4 OTH

AF:

0.198

Alfa

AF:

0.197

Hom.:

1108

Bravo

AF:

0.193

Asia WGS

AF:

0.187

AC:

653

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jul 02, 2018

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 16, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 16118333, 21222160) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Multiple endocrine neoplasia type 2B

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Pheochromocytoma

Benign:1

Feb 01, 2025

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Multiple endocrine neoplasia, type 2

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.0

DANN

Benign

0.74

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over