2-127337300-C-T

Variant names:

• chr2-127337300-C-T
• rs10496662
• NM_001371910.2:c.164+438G>A

Variant summary

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

The NM_001371910.2(MAP3K2):​c.164+438G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0367 in 152,196 control chromosomes in the GnomAD database, including 352 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 0.037 (352 hom., cov: 32)
• Consequence: MAP3K2 NM_001371910.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 1 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371910.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K2	NM_001371910.2	MANE Select	c.164+438G>A		intron	N/A	NP_001358839.1	Q9Y2U5
	MAP3K2	NM_001371911.1		c.164+438G>A		intron	N/A	NP_001358840.1	Q9Y2U5
	MAP3K2	NM_006609.5		c.164+438G>A		intron	N/A	NP_006600.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K2	ENST00000682094.1	MANE Select	c.164+438G>A		intron	N/A	ENSP00000507315.1	Q9Y2U5
	MAP3K2	ENST00000344908.9	TSL:1	c.164+438G>A		intron	N/A	ENSP00000343463.5	Q9Y2U5
	MAP3K2	ENST00000409947.5	TSL:1	c.164+438G>A		intron	N/A	ENSP00000387246.1	Q9Y2U5

Frequencies

GnomAD3 genomes AF: 0.0368 AC: 5592 AN: 152076 Hom.: 352 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.0263

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

GnomAD4 genome AF: 0.0367 AC: 5593 AN: 152196 Hom.: 352 Cov.: 32 AF XY: 0.0354 AC XY: 2637 AN XY: 74414

African (AFR) AF: 0.127 AC: 5272 AN: 41488

American (AMR) AF: 0.0143 AC: 219 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000471 AC: 32 AN: 68008

Other (OTH) AF: 0.0261 AC: 55 AN: 2110

Alfa AF: 0.0692 Hom.: 150

Bravo AF: 0.0425

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.71
DANN	Benign	0.67
PhyloP100		-1.3
Mutation Taster		=94/6	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: rs10496662; hg19: chr2-128094876;