chr15-66387126-T-TGC

Position:

• chr15-66387126-T-TGC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_002755.4(MAP2K1):​c.-216_-215dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00605 in 371,492 control chromosomes in the GnomAD database, including 50 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (47 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (3 hom.)
• Consequence: MAP2K1 NM_002755.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.818

Genes affected

MAP2K1 (HGNC:6840): (mitogen-activated protein kinase kinase 1) The protein encoded by this gene is a member of the dual specificity protein kinase family, which acts as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon wide variety of extra- and intracellular signals. As an essential component of MAP kinase signal transduction pathway, this kinase is involved in many cellular processes such as proliferation, differentiation, transcription regulation and development. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 15-66387126-T-TGC is Benign according to our data. Variant chr15-66387126-T-TGC is described in ClinVar as [Likely_benign]. Clinvar id is 316834.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP2K1	NM_002755.4	c.-216_-215dup		5_prime_UTR_variant	1/11	ENST00000307102.10	NP_002746.1
MAP2K1	XM_017022411.3	c.-216_-215dup		5_prime_UTR_variant	1/10		XP_016877900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP2K1	ENST00000307102.10	c.-216_-215dup		5_prime_UTR_variant	1/11	1	NM_002755.4	ENSP00000302486	P1

Frequencies

GnomAD3 genomes AF: 0.0132 AC: 1858 AN: 141064 Hom.: 47 Cov.: 33

Gnomad AFR AF: 0.0449

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00341

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00329

Gnomad NFE AF: 0.000187

Gnomad OTH AF: 0.00749

GnomAD4 exome AF: 0.00168 AC: 387 AN: 230294 Hom.: 3 Cov.: 2 AF XY: 0.00136 AC XY: 165 AN XY: 121652

Gnomad4 AFR exome AF: 0.0652

Gnomad4 AMR exome AF: 0.00298

Gnomad4 ASJ exome AF: 0.000357

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000752

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000207

Gnomad4 OTH exome AF: 0.00562

GnomAD4 genome AF: 0.0132 AC: 1862 AN: 141198 Hom.: 47 Cov.: 33 AF XY: 0.0127 AC XY: 870 AN XY: 68568

Gnomad4 AFR AF: 0.0449

Gnomad4 AMR AF: 0.00340

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000187

Gnomad4 OTH AF: 0.00740

Alfa AF: 0.0126 Hom.: 6

Bravo AF: 0.0144

Asia WGS AF: 0.00231 AC: 8 AN: 3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Cardio-facio-cutaneous syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 16, 2018

- -

Noonan syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs141005341; hg19: chr15-66679464;