17-69436244-T-G

Position:

• chr17-69436244-T-G

Variant summary

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

The NM_002758.4(MAP2K6):​c.16+21244T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 152,052 control chromosomes in the GnomAD database, including 30,150 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 0.62 (30150 hom., cov: 32)
• Consequence: MAP2K6 NM_002758.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.490

Genes affected

MAP2K6 (HGNC:6846): (mitogen-activated protein kinase kinase 6) This gene encodes a member of the dual specificity protein kinase family, which functions as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein phosphorylates and activates p38 MAP kinase in response to inflammatory cytokines or environmental stress. As an essential component of p38 MAP kinase mediated signal transduction pathway, this gene is involved in many cellular processes such as stress induced cell cycle arrest, transcription activation and apoptosis. [provided by RefSeq, Jul 2008]

MAP2K6 (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 (AFR) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP2K6	NM_002758.4	c.16+21244T>G		intron_variant		ENST00000590474.7	NP_002749.2
MAP2K6	XM_047436411.1	c.-153+20967T>G		intron_variant			XP_047292367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP2K6	ENST00000590474.7	c.16+21244T>G		intron_variant		1	NM_002758.4	ENSP00000468348.1
MAP2K6	ENST00000586641.5	n.290+21244T>G		intron_variant		1
MAP2K6	ENST00000359094.7	n.16+21244T>G		intron_variant		5		ENSP00000351997.3

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94168 AN: 151934 Hom.: 30103 Cov.: 32

Gnomad AFR AF: 0.778

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.620 AC: 94262 AN: 152052 Hom.: 30150 Cov.: 32 AF XY: 0.614 AC XY: 45606 AN XY: 74316

Gnomad4 AFR AF: 0.778

Gnomad4 AMR AF: 0.500

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.544

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.541

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.627

Alfa AF: 0.562 Hom.: 11057

Bravo AF: 0.628

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.2
DANN	Benign	0.63

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: rs817565; hg19: chr17-67432385;