15-67802747-G-A

Variant names:

• chr15-67802747-G-A
• rs1026732
• NM_145160.3:c.1243-3899G>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.1243-3899G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 152,168 control chromosomes in the GnomAD database, including 12,317 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 0.39 (12317 hom., cov: 33)
• Consequence: MAP2K5 NM_145160.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33
• Publications: 22 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP2K5	NM_145160.3	c.1243-3899G>A		intron_variant	Intron 21 of 21	ENST00000178640.10	NP_660143.1
MAP2K5	NM_002757.4	c.1213-3899G>A		intron_variant	Intron 20 of 20		NP_002748.1
MAP2K5	NM_001206804.2	c.1135-3899G>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.1243-3899G>A		intron_variant	Intron 21 of 21	1	NM_145160.3	ENSP00000178640.5

Frequencies

GnomAD3 genomes AF: 0.388 AC: 59037 AN: 152050 Hom.: 12277 Cov.: 33

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.389 AC: 59123 AN: 152168 Hom.: 12317 Cov.: 33 AF XY: 0.393 AC XY: 29239 AN XY: 74390

African (AFR) AF: 0.423 AC: 17577 AN: 41508

American (AMR) AF: 0.538 AC: 8228 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1567 AN: 3468

East Asian (EAS) AF: 0.696 AC: 3601 AN: 5172

South Asian (SAS) AF: 0.449 AC: 2167 AN: 4826

European-Finnish (FIN) AF: 0.301 AC: 3188 AN: 10584

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21668 AN: 68000

Other (OTH) AF: 0.401 AC: 848 AN: 2114

Alfa AF: 0.366 Hom.: 25576

Bravo AF: 0.411

Asia WGS AF: 0.564 AC: 1960 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0030
DANN	Benign	0.71
PhyloP100		-2.3
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: rs1026732; hg19: chr15-68095085;