rs884202

Variant names:

• chr15-67762050-G-A
• rs884202
• NM_145160.3:c.1135-7552G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_145160.3(MAP2K5):​c.1135-7552G>A variant causes a intron change. The variant allele was found at a frequency of 0.62 in 152,052 control chromosomes in the GnomAD database, including 29,979 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 0.62 (29979 hom., cov: 32)
• Consequence: MAP2K5 NM_145160.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.74
• Publications: 5 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP2K5	NM_145160.3	c.1135-7552G>A		intron_variant	Intron 19 of 21	ENST00000178640.10	NP_660143.1
MAP2K5	NM_002757.4	c.1105-7552G>A		intron_variant	Intron 18 of 20		NP_002748.1
MAP2K5	NM_001206804.2	c.1027-7552G>A		intron_variant	Intron 19 of 21		NP_001193733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP2K5	ENST00000178640.10	c.1135-7552G>A		intron_variant	Intron 19 of 21	1	NM_145160.3	ENSP00000178640.5

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94296 AN: 151934 Hom.: 29965 Cov.: 32

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.699

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.611

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

GnomAD4 genome AF: 0.620 AC: 94339 AN: 152052 Hom.: 29979 Cov.: 32 AF XY: 0.616 AC XY: 45815 AN XY: 74352

African (AFR) AF: 0.598 AC: 24805 AN: 41456

American (AMR) AF: 0.467 AC: 7139 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1893 AN: 3466

East Asian (EAS) AF: 0.372 AC: 1925 AN: 5174

South Asian (SAS) AF: 0.551 AC: 2656 AN: 4822

European-Finnish (FIN) AF: 0.699 AC: 7394 AN: 10574

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.682 AC: 46316 AN: 67960

Other (OTH) AF: 0.610 AC: 1289 AN: 2112

Alfa AF: 0.648 Hom.: 87376

Bravo AF: 0.598

Asia WGS AF: 0.462 AC: 1607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	18
DANN	Benign	0.76
PhyloP100		4.7
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: rs884202; hg19: chr15-68054388;