17-21303244-C-T

Position:

• chr17-21303244-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_145109.3(MAP2K3):​c.568+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (3183 hom., cov: 64)
  • Exomes 𝑓: 0.52 (30486 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAP2K3 NM_145109.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.16

Genes affected

MAP2K3 (HGNC:6843): (mitogen-activated protein kinase kinase 3) The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase is activated by mitogenic and environmental stress, and participates in the MAP kinase-mediated signaling cascade. It phosphorylates and thus activates MAPK14/p38-MAPK. This kinase can be activated by insulin, and is necessary for the expression of glucose transporter. Expression of RAS oncogene is found to result in the accumulation of the active form of this kinase, which thus leads to the constitutive activation of MAPK14, and confers oncogenic transformation of primary cells. The inhibition of this kinase is involved in the pathogenesis of Yersina pseudotuberculosis. Multiple alternatively spliced transcript variants that encode distinct isoforms have been reported for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 17-21303244-C-T is Benign according to our data. Variant chr17-21303244-C-T is described in ClinVar as [Benign]. Clinvar id is 768850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP2K3	NM_145109.3	c.568+10C>T		intron_variant		ENST00000342679.9	NP_659731.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP2K3	ENST00000342679.9	c.568+10C>T		intron_variant		1	NM_145109.3	ENSP00000345083	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 79130 AN: 151900 Hom.: 3185 Cov.: 64 FAILED QC

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.525

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.521 AC: 760215 AN: 1459468 Hom.: 30486 Cov.: 74 AF XY: 0.522 AC XY: 379029 AN XY: 726116

Gnomad4 AFR exome AF: 0.512

Gnomad4 AMR exome AF: 0.528

Gnomad4 ASJ exome AF: 0.523

Gnomad4 EAS exome AF: 0.530

Gnomad4 SAS exome AF: 0.546

Gnomad4 FIN exome AF: 0.527

Gnomad4 NFE exome AF: 0.518

Gnomad4 OTH exome AF: 0.522

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.521 AC: 79186 AN: 152016 Hom.: 3183 Cov.: 64 AF XY: 0.522 AC XY: 38796 AN XY: 74336

Gnomad4 AFR AF: 0.512

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.524

Gnomad4 EAS AF: 0.528

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.525

Gnomad4 NFE AF: 0.521

Gnomad4 OTH AF: 0.526

Alfa AF: 0.524 Hom.: 618

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.19
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs736103; hg19: chr17-21206556; COSMIC: COSV57567467; COSMIC: COSV57567467;