rs3088374

Positions:

• chr2-127304472-T-C
• chr2-127304472-T-G

Variant summary

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

The NM_001371910.2(MAP3K2):​c.*3107A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 151,918 control chromosomes in the GnomAD database, including 15,025 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 0.44 (15023 hom., cov: 32)
  • Exomes 𝑓: 0.31 (2 hom.)
• Consequence: MAP3K2 NM_001371910.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K2	NM_001371910.2	c.*3107A>G		3_prime_UTR_variant	17/17	ENST00000682094.1	NP_001358839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K2	ENST00000682094.1	c.*3107A>G		3_prime_UTR_variant	17/17		NM_001371910.2	ENSP00000507315.1
MAP3K2	ENST00000409947.5	c.*3107A>G		3_prime_UTR_variant	17/17	1		ENSP00000387246.1
ENSG00000286145	ENST00000651019.1	n.342+2583T>C		intron_variant
ENSG00000286145	ENST00000655875.1	n.357+2583T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66677 AN: 151772 Hom.: 15006 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.432

GnomAD4 exome AF: 0.308 AC: 8 AN: 26 Hom.: 2 Cov.: 0 AF XY: 0.250 AC XY: 3 AN XY: 12

Gnomad4 FIN exome AF: 0.318

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.439 AC: 66733 AN: 151892 Hom.: 15023 Cov.: 32 AF XY: 0.445 AC XY: 33039 AN XY: 74210

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.563

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.718

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.428

Alfa AF: 0.431 Hom.: 14000

Bravo AF: 0.452

Asia WGS AF: 0.516 AC: 1791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.2
DANN	Benign	0.83

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: rs3088374; hg19: chr2-128062048;