chr17-69444670-T-G

Variant names:

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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP2K6	NM_002758.4	c.16+29670T>G		intron_variant	Intron 1 of 11	ENST00000590474.7	NP_002749.2
MAP2K6	XM_047436411.1	c.-153+29393T>G		intron_variant	Intron 1 of 11		XP_047292367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP2K6	ENST00000590474.7	c.16+29670T>G		intron_variant	Intron 1 of 11	1	NM_002758.4	ENSP00000468348.1
MAP2K6	ENST00000586641.5	n.290+29670T>G		intron_variant	Intron 1 of 6	1
MAP2K6	ENST00000359094.7	n.16+29670T>G		intron_variant	Intron 1 of 11	5		ENSP00000351997.3

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

Gnomad4 AFR AF: 0.615

Gnomad4 AMR AF: 0.592

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.609

Gnomad4 SAS AF: 0.592

Gnomad4 FIN AF: 0.531

Gnomad4 NFE AF: 0.480

Gnomad4 OTH AF: 0.518

Alfa AF: 0.489 Hom.: 35955

Bravo AF: 0.548

Asia WGS AF: 0.603 AC: 2098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.3
DANN	Benign	0.78

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: rs1972933; hg19: chr17-67440811;