15-67779737-T-G

Variant names:

• chr15-67779737-T-G
• rs4489954
• NM_145160.3:c.1242+6985T>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.1242+6985T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 152,062 control chromosomes in the GnomAD database, including 31,666 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 0.64 (31666 hom., cov: 32)
• Consequence: MAP2K5 NM_145160.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.462
• Publications: 13 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP2K5	NM_145160.3	c.1242+6985T>G		intron_variant	Intron 21 of 21	ENST00000178640.10	NP_660143.1
MAP2K5	NM_002757.4	c.1212+6985T>G		intron_variant	Intron 20 of 20		NP_002748.1
MAP2K5	NM_001206804.2	c.1134+6985T>G		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.1242+6985T>G		intron_variant	Intron 21 of 21	1	NM_145160.3	ENSP00000178640.5

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96771 AN: 151944 Hom.: 31652 Cov.: 32

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.618

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

GnomAD4 genome AF: 0.637 AC: 96805 AN: 152062 Hom.: 31666 Cov.: 32 AF XY: 0.630 AC XY: 46851 AN XY: 74350

African (AFR) AF: 0.630 AC: 26126 AN: 41454

American (AMR) AF: 0.473 AC: 7223 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1956 AN: 3470

East Asian (EAS) AF: 0.298 AC: 1544 AN: 5174

South Asian (SAS) AF: 0.550 AC: 2649 AN: 4818

European-Finnish (FIN) AF: 0.724 AC: 7661 AN: 10578

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.698 AC: 47433 AN: 67978

Other (OTH) AF: 0.613 AC: 1290 AN: 2104

Alfa AF: 0.658 Hom.: 124929

Bravo AF: 0.614

Asia WGS AF: 0.412 AC: 1436 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.2
DANN	Benign	0.63
PhyloP100		0.46
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: rs4489954; hg19: chr15-68072075;