rs2241423

Positions:

• chr15-67794500-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.1243-12146G>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

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=-0.86).
• 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/exons	MANE	UniProt
MAP2K5	NM_145160.3	c.1243-12146G>A		intron_variant		ENST00000178640.10
MAP2K5	NM_001206804.2	c.1135-12146G>A		intron_variant
MAP2K5	NM_002757.4	c.1213-12146G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP2K5	ENST00000178640.10	c.1243-12146G>A		intron_variant		1	NM_145160.3	P1

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

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.594

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.310

Alfa AF: 0.252 Hom.: 12156

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

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: rs2241423; hg19: chr15-68086838;