chr2-135019934-A-G

Position:

• chr2-135019934-A-G

Variant summary

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

The NM_025052.5(MAP3K19):​c.138+1781T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,080 control chromosomes in the GnomAD database, including 6,062 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 0.25 (6062 hom., cov: 32)
• Consequence: MAP3K19 NM_025052.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.411

Genes affected

MAP3K19 (HGNC:26249): (mitogen-activated protein kinase kinase kinase 19) Predicted to enable ATP binding activity; protein serine kinase activity; and protein serine/threonine kinase activity. Predicted to be involved in protein phosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K19	NM_025052.5	c.138+1781T>C		intron_variant		ENST00000392915.7	NP_079328.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K19	ENST00000392915.7	c.138+1781T>C		intron_variant		5	NM_025052.5	ENSP00000376647	P2

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38408 AN: 151964 Hom.: 6052 Cov.: 32

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.253 AC: 38462 AN: 152080 Hom.: 6062 Cov.: 32 AF XY: 0.256 AC XY: 19025 AN XY: 74362

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.291

Alfa AF: 0.219 Hom.: 708

Bravo AF: 0.268

Asia WGS AF: 0.361 AC: 1254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.6
DANN	Benign	0.61

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: rs13390171; hg19: chr2-135777504;