rs7172298

chr15-67580645-T-C

Variant summary

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

The NM_145160.3(MAP2K5):c.253-109T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 727,766 control chromosomes in the GnomAD database, including 74,477 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 0.41 (14071 hom., cov: 32)
  • Exomes 𝑓: 0.44 (60406 hom.)
• Consequence: MAP2K5 NM_145160.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.10

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=-0.38).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP2K5	NM_145160.3	c.253-109T>C		intron_variant		ENST00000178640.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP2K5	ENST00000178640.10	c.253-109T>C		intron_variant		1	NM_145160.3	P1

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62865 AN: 151924 Hom.: 14071 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.0840

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.395

GnomAD4 exome AF: 0.438 AC: 252036 AN: 575724 Hom.: 60406 AF XY: 0.437 AC XY: 137558 AN XY: 315034

Gnomad4 AFR exome AF: 0.308

Gnomad4 AMR exome AF: 0.245

Gnomad4 ASJ exome AF: 0.377

Gnomad4 EAS exome AF: 0.0639

Gnomad4 SAS exome AF: 0.348

Gnomad4 FIN exome AF: 0.516

Gnomad4 NFE exome AF: 0.514

Gnomad4 OTH exome AF: 0.444

GnomAD4 genome AF: 0.413 AC: 62861 AN: 152042 Hom.: 14071 Cov.: 32 AF XY: 0.405 AC XY: 30048 AN XY: 74280

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.0840

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.389

Alfa AF: 0.477 Hom.: 7846

Bravo AF: 0.393

Asia WGS AF: 0.208 AC: 730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
Cadd	Benign	19
Dann	Benign	0.79

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: rs7172298; hg19: chr15-67872983; COSMIC: COSV51614168;