17-69444670-T-G

Variant names:

• chr17-69444670-T-G
• rs1972933
• NM_002758.4:c.16+29670T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002758.4(MAP2K6):​c.16+29670T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 152,024 control chromosomes in the GnomAD database, including 22,552 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 0.54 (22552 hom., cov: 32)
• Consequence: MAP2K6 NM_002758.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.414
• Publications: 4 publications found

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]

ENSG00000298981 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002758.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP2K6	NM_002758.4	MANE Select	c.16+29670T>G		intron	N/A	NP_002749.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP2K6	ENST00000590474.7	TSL:1 MANE Select	c.16+29670T>G		intron	N/A	ENSP00000468348.1
	MAP2K6	ENST00000586641.5	TSL:1	n.290+29670T>G		intron	N/A
	MAP2K6	ENST00000928053.1		c.16+29670T>G		intron	N/A	ENSP00000598112.1

Frequencies

GnomAD3 genomes AF: 0.540 AC: 81993 AN: 151906 Hom.: 22515 Cov.: 32

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.514

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

GnomAD4 genome AF: 0.540 AC: 82087 AN: 152024 Hom.: 22552 Cov.: 32 AF XY: 0.545 AC XY: 40498 AN XY: 74322

African (AFR) AF: 0.615 AC: 25494 AN: 41486

American (AMR) AF: 0.592 AC: 9036 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1726 AN: 3470

East Asian (EAS) AF: 0.609 AC: 3147 AN: 5164

South Asian (SAS) AF: 0.592 AC: 2846 AN: 4806

European-Finnish (FIN) AF: 0.531 AC: 5609 AN: 10570

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.480 AC: 32637 AN: 67942

Other (OTH) AF: 0.518 AC: 1090 AN: 2106

Alfa AF: 0.498 Hom.: 78602

Bravo AF: 0.548

Asia WGS AF: 0.603 AC: 2098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.3
DANN	Benign	0.78
PhyloP100		-0.41
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: rs1972933; hg19: chr17-67440811;