15-67779737-T-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.82).
• 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/exons	MANE	UniProt
MAP2K5	NM_145160.3	c.1242+6985T>G		intron_variant		ENST00000178640.10
MAP2K5	NM_001206804.2	c.1134+6985T>G		intron_variant
MAP2K5	NM_002757.4	c.1212+6985T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP2K5	ENST00000178640.10	c.1242+6985T>G		intron_variant		1	NM_145160.3	P1

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

Gnomad4 AFR AF: 0.630

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.564

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.724

Gnomad4 NFE AF: 0.698

Gnomad4 OTH AF: 0.613

Alfa AF: 0.656 Hom.: 59384

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

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: rs4489954; hg19: chr15-68072075;