rs2241423

Variant names:

• chr15-67794500-G-A
• rs2241423
• NM_145160.3:c.1243-12146G>A

Variant summary

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

The NM_145160.3(MAP2K5):​c.1243-12146G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 151,902 control chromosomes in the GnomAD database, including 7,804 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 (7804 hom., cov: 31)
• Consequence: MAP2K5 NM_145160.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730
• Publications: 168 publications found

Genes affected

MAP2K5 (HGNC:6845): (mitogen-activated protein kinase kinase 5) The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase specifically interacts with and activates MAPK7/ERK5. This kinase itself can be phosphorylated and activated by MAP3K3/MEKK3, as well as by atypical protein kinase C isoforms (aPKCs). The signal cascade mediated by this kinase is involved in growth factor stimulated cell proliferation and muscle cell differentiation. Three alternatively spliced transcript variants of this gene encoding distinct isoforms have been described. [provided by RefSeq, May 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP2K5	NM_145160.3	c.1243-12146G>A		intron_variant	Intron 21 of 21	ENST00000178640.10	NP_660143.1
MAP2K5	NM_002757.4	c.1213-12146G>A		intron_variant	Intron 20 of 20		NP_002748.1
MAP2K5	NM_001206804.2	c.1135-12146G>A		intron_variant	Intron 21 of 21		NP_001193733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP2K5	ENST00000178640.10	c.1243-12146G>A		intron_variant	Intron 21 of 21	1	NM_145160.3	ENSP00000178640.5

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45308 AN: 151780 Hom.: 7775 Cov.: 31

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.299 AC: 45384 AN: 151902 Hom.: 7804 Cov.: 31 AF XY: 0.299 AC XY: 22212 AN XY: 74238

African (AFR) AF: 0.373 AC: 15434 AN: 41380

American (AMR) AF: 0.434 AC: 6623 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1253 AN: 3470

East Asian (EAS) AF: 0.594 AC: 3069 AN: 5166

South Asian (SAS) AF: 0.350 AC: 1685 AN: 4812

European-Finnish (FIN) AF: 0.148 AC: 1559 AN: 10550

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14911 AN: 67958

Other (OTH) AF: 0.310 AC: 653 AN: 2104

Alfa AF: 0.262 Hom.: 26388

Bravo AF: 0.327

Asia WGS AF: 0.495 AC: 1719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.0
DANN	Benign	0.62
PhyloP100		0.073
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: rs2241423; hg19: chr15-68086838;