15-67750719-C-G

Variant names:

• chr15-67750719-C-G
• rs8028313
• NM_145160.3:c.1134+2118C>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.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
• Publications: 27 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=-0.81).
• 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 rank	MANE	Protein	UniProt
MAP2K5	NM_145160.3	c.1134+2118C>G		intron_variant	Intron 19 of 21	ENST00000178640.10	NP_660143.1
MAP2K5	NM_002757.4	c.1104+2118C>G		intron_variant	Intron 18 of 20		NP_002748.1
MAP2K5	NM_001206804.2	c.1026+2118C>G		intron_variant	Intron 19 of 21		NP_001193733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP2K5	ENST00000178640.10	c.1134+2118C>G		intron_variant	Intron 19 of 21	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

African (AFR) AF: 0.319 AC: 13205 AN: 41438

American (AMR) AF: 0.424 AC: 6474 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1255 AN: 3472

East Asian (EAS) AF: 0.525 AC: 2707 AN: 5156

South Asian (SAS) AF: 0.354 AC: 1705 AN: 4818

European-Finnish (FIN) AF: 0.148 AC: 1561 AN: 10558

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14785 AN: 67986

Other (OTH) AF: 0.291 AC: 615 AN: 2114

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
PhyloP100		0.28
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: rs8028313; hg19: chr15-68043057;