rs754967305

Variant names:

• chr10-43100733-C-A
• rs754967305
• NM_020975.6:c.337+11C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-43100733-C-A
• chr10-43100733-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_020975.6(RET):​c.337+11C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RET NM_020975.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.15
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• familial medullary thyroid carcinoma

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• multiple endocrine neoplasia type 2A

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P
• multiple endocrine neoplasia type 2B

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
• pheochromocytoma

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• Hirschsprung disease, susceptibility to, 1

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Haddad syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Hirschsprung disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• renal agenesis, unilateral

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• bilateral renal agenesis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• renal agenesis

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 10-43100733-C-A is Benign according to our data. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43100733-C-A is described in CliVar as Likely_benign. Clinvar id is 1548718.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RET	NM_020975.6	c.337+11C>A		intron_variant	Intron 2 of 19	ENST00000355710.8	NP_066124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RET	ENST00000355710.8	c.337+11C>A		intron_variant	Intron 2 of 19	5	NM_020975.6	ENSP00000347942.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1429620 Hom.: 0 Cov.: 43 AF XY: 0.00 AC XY: 0 AN XY: 708006

African (AFR) AF: 0.00 AC: 0 AN: 33022

American (AMR) AF: 0.00 AC: 0 AN: 40174

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25456

East Asian (EAS) AF: 0.00 AC: 0 AN: 38504

South Asian (SAS) AF: 0.00 AC: 0 AN: 82132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49700

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4602

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1096940

Other (OTH) AF: 0.00 AC: 0 AN: 59090

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Multiple endocrine neoplasia, type 2 Benign:1

Oct 09, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely 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	-0.96
CADD	Benign	0.0050
DANN	Benign	0.66
PhyloP100		-2.1
PromoterAI		-0.067	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs754967305; hg19: chr10-43596181;