rs1026732

Positions:

• chr15-67802747-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MAP2K5	NM_145160.3	c.1243-3899G>A		intron_variant		ENST00000178640.10	NP_660143.1
MAP2K5	NM_001206804.2	c.1135-3899G>A		intron_variant			NP_001193733.1
MAP2K5	NM_002757.4	c.1213-3899G>A		intron_variant			NP_002748.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP2K5	ENST00000178640.10	c.1243-3899G>A		intron_variant		1	NM_145160.3	ENSP00000178640	P1

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

Gnomad4 AFR AF: 0.423

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.696

Gnomad4 SAS AF: 0.449

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.401

Alfa AF: 0.358 Hom.: 15271

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1026732; hg19: chr15-68095085;