rs2876981

Variant names:

• chr22-21851322-A-C
• rs2876981
• NM_002745.5:c.119+16000T>G

Your query was ambiguous. Multiple possible variants found:

• chr22-21851322-A-C
• chr22-21851322-A-G

Variant summary

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

The NM_002745.5(MAPK1):​c.119+16000T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 152,074 control chromosomes in the GnomAD database, including 7,579 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 0.30 (7579 hom., cov: 30)
• Consequence: MAPK1 NM_002745.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.621
• Publications: 13 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002745.5. 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.119+16000T>G		intron	N/A	NP_002736.3
	MAPK1	NM_138957.3		c.119+16000T>G		intron	N/A	NP_620407.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK1	ENST00000215832.11	TSL:1 MANE Select	c.119+16000T>G		intron	N/A	ENSP00000215832.7
	MAPK1	ENST00000398822.7	TSL:1	c.119+16000T>G		intron	N/A	ENSP00000381803.3
	MAPK1	ENST00000544786.1	TSL:1	c.119+16000T>G		intron	N/A	ENSP00000440842.1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45922 AN: 151956 Hom.: 7579 Cov.: 30

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.302 AC: 45926 AN: 152074 Hom.: 7579 Cov.: 30 AF XY: 0.294 AC XY: 21870 AN XY: 74344

African (AFR) AF: 0.198 AC: 8201 AN: 41488

American (AMR) AF: 0.304 AC: 4634 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1523 AN: 3464

East Asian (EAS) AF: 0.100 AC: 521 AN: 5186

South Asian (SAS) AF: 0.216 AC: 1042 AN: 4826

European-Finnish (FIN) AF: 0.268 AC: 2838 AN: 10576

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.382 AC: 25970 AN: 67970

Other (OTH) AF: 0.347 AC: 730 AN: 2106

Alfa AF: 0.340 Hom.: 4867

Bravo AF: 0.301

Asia WGS AF: 0.156 AC: 543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.1
DANN	Benign	0.57
PhyloP100		0.62
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: rs2876981; hg19: chr22-22205611;