15-67750719-C-G

Position:

• chr15-67750719-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145160.3(MAP2K5):​c.1134+2118C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,022 control chromosomes in the GnomAD database, including 6,748 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 0.28 (6748 hom., cov: 31)
• Consequence: MAP2K5 NM_145160.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280

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]

MAP2K5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP2K5	NM_145160.3	c.1134+2118C>G		intron_variant		ENST00000178640.10	NP_660143.1
MAP2K5	NM_002757.4	c.1104+2118C>G		intron_variant			NP_002748.1
MAP2K5	NM_001206804.2	c.1026+2118C>G		intron_variant			NP_001193733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP2K5	ENST00000178640.10	c.1134+2118C>G		intron_variant		1	NM_145160.3	ENSP00000178640.5

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42442 AN: 151904 Hom.: 6727 Cov.: 31

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.280 AC: 42504 AN: 152022 Hom.: 6748 Cov.: 31 AF XY: 0.281 AC XY: 20846 AN XY: 74292

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.525

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.291

Alfa AF: 0.117 Hom.: 164

Bravo AF: 0.305

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.9
DANN	Benign	0.68

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: rs8028313; hg19: chr15-68043057;