rs2278076

Variant names:

• chr15-67807262-G-A
• rs2278076
• NM_145160.3:c.*512G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-67807262-G-A
• chr15-67807262-G-C

Variant summary

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

The NM_145160.3(MAP2K5):​c.*512G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 206,572 control chromosomes in the GnomAD database, including 6,650 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 0.21 (4598 hom., cov: 33)
  • Exomes 𝑓: 0.24 (2052 hom.)
• Consequence: MAP2K5 NM_145160.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP2K5	NM_145160.3	c.*512G>A		downstream_gene_variant		ENST00000178640.10	NP_660143.1
MAP2K5	NM_002757.4	c.*512G>A		downstream_gene_variant			NP_002748.1
MAP2K5	NM_001206804.2	c.*512G>A		downstream_gene_variant			NP_001193733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP2K5	ENST00000178640.10	c.*512G>A		downstream_gene_variant		1	NM_145160.3	ENSP00000178640.5

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32137 AN: 152034 Hom.: 4581 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.241

GnomAD4 exome AF: 0.238 AC: 12940 AN: 54418 Hom.: 2052 AF XY: 0.246 AC XY: 7087 AN XY: 28820

Gnomad4 AFR exome AF: 0.100

Gnomad4 AMR exome AF: 0.497

Gnomad4 ASJ exome AF: 0.297

Gnomad4 EAS exome AF: 0.578

Gnomad4 SAS exome AF: 0.303

Gnomad4 FIN exome AF: 0.115

Gnomad4 NFE exome AF: 0.180

Gnomad4 OTH exome AF: 0.210

GnomAD4 genome AF: 0.211 AC: 32167 AN: 152154 Hom.: 4598 Cov.: 33 AF XY: 0.216 AC XY: 16038 AN XY: 74388

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.593

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.244

Alfa AF: 0.209 Hom.: 396

Bravo AF: 0.232

Asia WGS AF: 0.468 AC: 1627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.72

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2278076; hg19: chr15-68099600;