rs868037

Positions:

• chr15-67762658-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_145160.3(MAP2K5):​c.1135-6944A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 151,408 control chromosomes in the GnomAD database, including 29,634 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 0.62 (29634 hom., cov: 31)
• Consequence: MAP2K5 NM_145160.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP2K5	NM_145160.3	c.1135-6944A>G		intron_variant		ENST00000178640.10
MAP2K5	NM_001206804.2	c.1027-6944A>G		intron_variant
MAP2K5	NM_002757.4	c.1105-6944A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP2K5	ENST00000178640.10	c.1135-6944A>G		intron_variant		1	NM_145160.3	P1

Frequencies

GnomAD3 genomes AF: 0.619 AC: 93611 AN: 151290 Hom.: 29620 Cov.: 31

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.806

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.619 AC: 93653 AN: 151408 Hom.: 29634 Cov.: 31 AF XY: 0.614 AC XY: 45410 AN XY: 73974

Gnomad4 AFR AF: 0.596

Gnomad4 AMR AF: 0.466

Gnomad4 ASJ AF: 0.541

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.693

Gnomad4 NFE AF: 0.680

Gnomad4 OTH AF: 0.608

Alfa AF: 0.619 Hom.: 5593

Bravo AF: 0.598

Asia WGS AF: 0.460 AC: 1598 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	12
DANN	Benign	0.83

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: rs868037; hg19: chr15-68054996;