15-67745240-A-G

Variant names:

• chr15-67745240-A-G
• rs11635424
• NM_145160.3:c.1075-2991A>G

Variant summary

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

The NM_145160.3(MAP2K5):​c.1075-2991A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 152,058 control chromosomes in the GnomAD database, including 23,569 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 0.53 (23569 hom., cov: 32)
• Consequence: MAP2K5 NM_145160.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.772
• Publications: 17 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP2K5	NM_145160.3	c.1075-2991A>G		intron_variant	Intron 17 of 21	ENST00000178640.10	NP_660143.1
MAP2K5	NM_002757.4	c.1045-2991A>G		intron_variant	Intron 16 of 20		NP_002748.1
MAP2K5	NM_001206804.2	c.967-2991A>G		intron_variant	Intron 17 of 21		NP_001193733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP2K5	ENST00000178640.10	c.1075-2991A>G		intron_variant	Intron 17 of 21	1	NM_145160.3	ENSP00000178640.5

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80204 AN: 151940 Hom.: 23574 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.537

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

GnomAD4 genome AF: 0.527 AC: 80197 AN: 152058 Hom.: 23569 Cov.: 32 AF XY: 0.525 AC XY: 39000 AN XY: 74320

African (AFR) AF: 0.287 AC: 11919 AN: 41474

American (AMR) AF: 0.429 AC: 6542 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1852 AN: 3468

East Asian (EAS) AF: 0.364 AC: 1881 AN: 5168

South Asian (SAS) AF: 0.548 AC: 2641 AN: 4820

European-Finnish (FIN) AF: 0.688 AC: 7276 AN: 10574

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 46047 AN: 67974

Other (OTH) AF: 0.534 AC: 1128 AN: 2114

Alfa AF: 0.610 Hom.: 50074

Bravo AF: 0.492

Asia WGS AF: 0.409 AC: 1424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.54
PhyloP100		-0.77
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: rs11635424; hg19: chr15-68037578;