15-67766565-A-G

Variant names:

• chr15-67766565-A-G
• rs11071959
• NM_145160.3:c.1135-3037A>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.1135-3037A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,146 control chromosomes in the GnomAD database, including 6,675 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 0.29 (6675 hom., cov: 33)
• Consequence: MAP2K5 NM_145160.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.677
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145160.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP2K5	NM_145160.3	MANE Select	c.1135-3037A>G		intron	N/A	NP_660143.1	Q13163-1
	MAP2K5	NM_002757.4		c.1105-3037A>G		intron	N/A	NP_002748.1	Q13163-2
	MAP2K5	NM_001206804.2		c.1027-3037A>G		intron	N/A	NP_001193733.1	Q13163-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP2K5	ENST00000178640.10	TSL:1 MANE Select	c.1135-3037A>G		intron	N/A	ENSP00000178640.5	Q13163-1
	MAP2K5	ENST00000395476.6	TSL:1	c.1105-3037A>G		intron	N/A	ENSP00000378859.2	Q13163-2
	MAP2K5	ENST00000952141.1		c.1261-157A>G		intron	N/A	ENSP00000622200.1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43522 AN: 152028 Hom.: 6666 Cov.: 33

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.286 AC: 43564 AN: 152146 Hom.: 6675 Cov.: 33 AF XY: 0.288 AC XY: 21431 AN XY: 74382

African (AFR) AF: 0.393 AC: 16302 AN: 41500

American (AMR) AF: 0.183 AC: 2801 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 702 AN: 3470

East Asian (EAS) AF: 0.317 AC: 1638 AN: 5172

South Asian (SAS) AF: 0.344 AC: 1661 AN: 4826

European-Finnish (FIN) AF: 0.267 AC: 2831 AN: 10586

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16723 AN: 67982

Other (OTH) AF: 0.255 AC: 540 AN: 2114

Alfa AF: 0.248 Hom.: 8482

Bravo AF: 0.280

Asia WGS AF: 0.305 AC: 1061 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.3
DANN	Benign	0.58
PhyloP100		0.68
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: rs11071959; hg19: chr15-68058903;