2-127313427-C-T

Variant names:

• chr2-127313427-C-T
• rs6731176
• NM_001371910.2:c.1456+1327G>A

Variant summary

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

The NM_001371910.2(MAP3K2):​c.1456+1327G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,026 control chromosomes in the GnomAD database, including 14,458 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 0.43 (14458 hom., cov: 32)
• Consequence: MAP3K2 NM_001371910.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.56

Genes affected

MAP3K2 (HGNC:6854): (mitogen-activated protein kinase kinase kinase 2) The protein encoded by this gene is a member of serine/threonine protein kinase family. This kinase preferentially activates other kinases involved in the MAP kinase signaling pathway. This kinase has been shown to directly phosphorylate and activate Ikappa B kinases, and thus plays a role in NF-kappa B signaling pathway. This kinase has also been found to bind and activate protein kinase C-related kinase 2, which suggests its involvement in a regulated signaling process. [provided by RefSeq, Jul 2008]

ENSG00000286145 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K2	NM_001371910.2	c.1456+1327G>A		intron_variant	Intron 15 of 16	ENST00000682094.1	NP_001358839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K2	ENST00000682094.1	c.1456+1327G>A		intron_variant	Intron 15 of 16		NM_001371910.2	ENSP00000507315.1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65507 AN: 151906 Hom.: 14432 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.431 AC: 65577 AN: 152026 Hom.: 14458 Cov.: 32 AF XY: 0.434 AC XY: 32267 AN XY: 74308

Gnomad4 AFR AF: 0.399

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.617

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.429

Alfa AF: 0.435 Hom.: 5870

Bravo AF: 0.447

Asia WGS AF: 0.452 AC: 1567 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.034
DANN	Benign	0.67

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: rs6731176; hg19: chr2-128071003;