rs8101696

Positions:

• chr19-4115454-G-A
• chr19-4115454-G-C

Variant summary

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

The NM_030662.4(MAP2K2):​c.303+1965C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0558 in 152,258 control chromosomes in the GnomAD database, including 256 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 0.056 (256 hom., cov: 32)
• Consequence: MAP2K2 NM_030662.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.900

Genes affected

MAP2K2 (HGNC:6842): (mitogen-activated protein kinase kinase 2) The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase is known to play a critical role in mitogen growth factor signal transduction. It phosphorylates and thus activates MAPK1/ERK2 and MAPK2/ERK3. The activation of this kinase itself is dependent on the Ser/Thr phosphorylation by MAP kinase kinase kinases. Mutations in this gene cause cardiofaciocutaneous syndrome (CFC syndrome), a disease characterized by heart defects, cognitive disability, and distinctive facial features similar to those found in Noonan syndrome. The inhibition or degradation of this kinase is also found to be involved in the pathogenesis of Yersinia and anthrax. A pseudogene, which is located on chromosome 7, has been identified for this gene. [provided by RefSeq, Jul 2008]

MAP2K2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP2K2	NM_030662.4	c.303+1965C>T		intron_variant		ENST00000262948.10	NP_109587.1
MAP2K2	XM_006722799.3	c.303+1965C>T		intron_variant			XP_006722862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP2K2	ENST00000262948.10	c.303+1965C>T		intron_variant		1	NM_030662.4	ENSP00000262948.4
MAP2K2	ENST00000394867.9	n.742+1965C>T		intron_variant		5
MAP2K2	ENST00000599345.1	n.500+1965C>T		intron_variant		5
MAP2K2	ENST00000687128.1	n.742+1965C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0558 AC: 8495 AN: 152140 Hom.: 256 Cov.: 32

Gnomad AFR AF: 0.0491

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0374

Gnomad ASJ AF: 0.0493

Gnomad EAS AF: 0.0190

Gnomad SAS AF: 0.0692

Gnomad FIN AF: 0.0710

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0645

Gnomad OTH AF: 0.0541

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

GnomAD4 genome AF: 0.0558 AC: 8498 AN: 152258 Hom.: 256 Cov.: 32 AF XY: 0.0547 AC XY: 4076 AN XY: 74454

Gnomad4 AFR AF: 0.0490

Gnomad4 AMR AF: 0.0373

Gnomad4 ASJ AF: 0.0493

Gnomad4 EAS AF: 0.0191

Gnomad4 SAS AF: 0.0697

Gnomad4 FIN AF: 0.0710

Gnomad4 NFE AF: 0.0645

Gnomad4 OTH AF: 0.0535

Alfa AF: 0.0602 Hom.: 62

Bravo AF: 0.0523

Asia WGS AF: 0.0380 AC: 134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.072
DANN	Benign	0.43

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: rs8101696; hg19: chr19-4115452;