15-67676883-G-T

Position:

• chr15-67676883-G-T

Variant summary

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

The NM_145160.3(MAP2K5):​c.847+12238G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 152,080 control chromosomes in the GnomAD database, including 50,834 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 0.82 (50834 hom., cov: 31)
• Consequence: MAP2K5 NM_145160.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.695

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP2K5	NM_145160.3	c.847+12238G>T		intron_variant		ENST00000178640.10	NP_660143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP2K5	ENST00000178640.10	c.847+12238G>T		intron_variant		1	NM_145160.3	ENSP00000178640.5

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124073 AN: 151964 Hom.: 50812 Cov.: 31

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.875

Gnomad ASJ AF: 0.846

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.832

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.830

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

GnomAD4 genome AF: 0.816 AC: 124137 AN: 152080 Hom.: 50834 Cov.: 31 AF XY: 0.814 AC XY: 60545 AN XY: 74336

Gnomad4 AFR AF: 0.746

Gnomad4 AMR AF: 0.875

Gnomad4 ASJ AF: 0.846

Gnomad4 EAS AF: 0.768

Gnomad4 SAS AF: 0.833

Gnomad4 FIN AF: 0.806

Gnomad4 NFE AF: 0.848

Gnomad4 OTH AF: 0.823

Alfa AF: 0.829 Hom.: 11609

Bravo AF: 0.818

Asia WGS AF: 0.782 AC: 2721 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	9.2
DANN	Benign	0.66

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: rs8037887; hg19: chr15-67969221;