rs2266966

Variant names:

• chr22-21767265-T-C
• rs2266966
• NM_002745.5:c.*9+1930A>G

Your query was ambiguous. Multiple possible variants found:

• chr22-21767265-T-C
• chr22-21767265-T-G

Variant summary

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

The ENST00000215832.11(MAPK1):​c.*9+1930A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 152,112 control chromosomes in the GnomAD database, including 11,216 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 0.38 (11216 hom., cov: 32)
• Consequence: MAPK1 ENST00000215832.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• Publications: 16 publications found

Genes affected

MAPK1 (HGNC:6871): (mitogen-activated protein kinase 1) This gene encodes a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. The activation of this kinase requires its phosphorylation by upstream kinases. Upon activation, this kinase translocates to the nucleus of the stimulated cells, where it phosphorylates nuclear targets. One study also suggests that this protein acts as a transcriptional repressor independent of its kinase activity. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Two alternatively spliced transcript variants encoding the same protein, but differing in the UTRs, have been reported for this gene. [provided by RefSeq, Jan 2014]

MAPK1 Gene-Disease associations (from GenCC):

• Noonan syndrome 13

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000215832.11. 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
	MAPK1	NM_002745.5	MANE Select	c.*9+1930A>G		intron	N/A	NP_002736.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK1	ENST00000215832.11	TSL:1 MANE Select	c.*9+1930A>G		intron	N/A	ENSP00000215832.7
	MAPK1	ENST00000491588.1	TSL:2	n.234+1930A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57758 AN: 151994 Hom.: 11218 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.430

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.380 AC: 57781 AN: 152112 Hom.: 11216 Cov.: 32 AF XY: 0.372 AC XY: 27677 AN XY: 74368

African (AFR) AF: 0.347 AC: 14388 AN: 41486

American (AMR) AF: 0.387 AC: 5919 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1694 AN: 3470

East Asian (EAS) AF: 0.208 AC: 1074 AN: 5166

South Asian (SAS) AF: 0.326 AC: 1576 AN: 4828

European-Finnish (FIN) AF: 0.287 AC: 3035 AN: 10580

Middle Eastern (MID) AF: 0.473 AC: 138 AN: 292

European-Non Finnish (NFE) AF: 0.422 AC: 28664 AN: 67982

Other (OTH) AF: 0.427 AC: 903 AN: 2114

Alfa AF: 0.377 Hom.: 5929

Bravo AF: 0.386

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.31
DANN	Benign	0.28
PhyloP100		-1.5
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: rs2266966; hg19: chr22-22121554;