rs72751410

Variant names:

• chr15-67696248-A-G
• rs72751410
• NM_145160.3:c.972+2680A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_145160.3(MAP2K5):​c.972+2680A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00569 in 152,044 control chromosomes in the GnomAD database, including 5 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 0.0057 (5 hom., cov: 31)
• Consequence: MAP2K5 NM_145160.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680
• Publications: 1 publications found

Genes affected

MAP2K5 (HGNC:6845): (mitogen-activated protein kinase kinase 5) The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase specifically interacts with and activates MAPK7/ERK5. This kinase itself can be phosphorylated and activated by MAP3K3/MEKK3, as well as by atypical protein kinase C isoforms (aPKCs). The signal cascade mediated by this kinase is involved in growth factor stimulated cell proliferation and muscle cell differentiation. Three alternatively spliced transcript variants of this gene encoding distinct isoforms have been described. [provided by RefSeq, May 2011]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS2: High AC in GnomAd4 at 865 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP2K5	NM_145160.3	c.972+2680A>G		intron_variant	Intron 15 of 21	ENST00000178640.10	NP_660143.1
MAP2K5	NM_002757.4	c.972+2680A>G		intron_variant	Intron 15 of 20		NP_002748.1
MAP2K5	NM_001206804.2	c.864+2680A>G		intron_variant	Intron 15 of 21		NP_001193733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP2K5	ENST00000178640.10	c.972+2680A>G		intron_variant	Intron 15 of 21	1	NM_145160.3	ENSP00000178640.5

Frequencies

GnomAD3 genomes AF: 0.00570 AC: 866 AN: 151926 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.00194

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00302

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00123

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0104

Gnomad OTH AF: 0.00335

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

GnomAD4 genome AF: 0.00569 AC: 865 AN: 152044 Hom.: 5 Cov.: 31 AF XY: 0.00491 AC XY: 365 AN XY: 74308

African (AFR) AF: 0.00193 AC: 80 AN: 41460

American (AMR) AF: 0.00302 AC: 46 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 8 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00123 AC: 13 AN: 10550

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0104 AC: 704 AN: 68002

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00615 Hom.: 0

Bravo AF: 0.00567

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.65
DANN	Benign	0.76
PhyloP100		-0.068

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: rs72751410; hg19: chr15-67988586;