1-206685280-G-C

Position:

• chr1-206685280-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_032960.4(MAPKAPK2):​c.51G>C​(p.Pro17=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 27)
  • Exomes 𝑓: 0.049 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAPKAPK2 NM_032960.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0890

Genes affected

MAPKAPK2 (HGNC:6887): (MAPK activated protein kinase 2) This gene encodes a member of the Ser/Thr protein kinase family. This kinase is regulated through direct phosphorylation by p38 MAP kinase. In conjunction with p38 MAP kinase, this kinase is known to be involved in many cellular processes including stress and inflammatory responses, nuclear export, gene expression regulation and cell proliferation. Heat shock protein HSP27 was shown to be one of the substrates of this kinase in vivo. Two transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-206685280-G-C is Benign according to our data. Variant chr1-206685280-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 769547.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.089 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPKAPK2	NM_032960.4	c.51G>C	p.Pro17=	synonymous_variant	1/10	ENST00000367103.4	NP_116584.2
MAPKAPK2	NM_004759.5	c.51G>C	p.Pro17=	synonymous_variant	1/10		NP_004750.1
MAPKAPK2	XM_005273353.4	c.51G>C	p.Pro17=	synonymous_variant	1/11		XP_005273410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPKAPK2	ENST00000367103.4	c.51G>C	p.Pro17=	synonymous_variant	1/10	1	NM_032960.4	ENSP00000356070	P1
MAPKAPK2	ENST00000294981.8	c.51G>C	p.Pro17=	synonymous_variant	1/10	1		ENSP00000294981

Frequencies

GnomAD3 genomes AF: 0.00 AC: 19 AN: 118726 Hom.: 0 Cov.: 27 FAILED QC

Gnomad AFR AF: 0.0000615

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000801

Gnomad ASJ AF: 0.000343

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000653

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000185

Gnomad OTH AF: 0.000616

GnomAD3 exomes AF: 0.00301 AC: 56 AN: 18612 Hom.: 0 AF XY: 0.00292 AC XY: 32 AN XY: 10952

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00940

Gnomad NFE exome AF: 0.000354

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0494 AC: 4088 AN: 82754 Hom.: 1 Cov.: 3 AF XY: 0.0467 AC XY: 2214 AN XY: 47360

Gnomad4 AFR exome AF: 0.0449

Gnomad4 AMR exome AF: 0.0248

Gnomad4 ASJ exome AF: 0.0365

Gnomad4 EAS exome AF: 0.0540

Gnomad4 SAS exome AF: 0.0196

Gnomad4 FIN exome AF: 0.0349

Gnomad4 NFE exome AF: 0.0590

Gnomad4 OTH exome AF: 0.0523

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000160 AC: 19 AN: 118792 Hom.: 0 Cov.: 27 AF XY: 0.000173 AC XY: 10 AN XY: 57768

Gnomad4 AFR AF: 0.0000613

Gnomad4 AMR AF: 0.0000800

Gnomad4 ASJ AF: 0.000343

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000653

Gnomad4 NFE AF: 0.000185

Gnomad4 OTH AF: 0.000610

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 20, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.5
DANN	Benign	0.76

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: rs1402681700; hg19: chr1-206858625;