2-241114131-C-G

Variant names:

• chr2-241114131-C-G
• rs17382723
• ENST00000493544.1:n.4678G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000493544.1(PASK):​n.4678G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 984,670 control chromosomes in the GnomAD database, including 21,689 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 0.18 (2735 hom., cov: 33)
  • Exomes 𝑓: 0.21 (18954 hom.)
• Consequence: PASK ENST00000493544.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.298
• Publications: 6 publications found

Genes affected

PASK (HGNC:17270): (PAS domain containing serine/threonine kinase) This gene encodes a member of the serine/threonine kinase family that contains two PAS domains. Expression of this gene is regulated by glucose, and the encoded protein plays a role in the regulation of insulin gene expression. Downregulation of this gene may play a role in type 2 diabetes. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PASK	NM_015148.4	c.3333+912G>C		intron_variant	Intron 14 of 17	ENST00000234040.9	NP_055963.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PASK	ENST00000234040.9	c.3333+912G>C		intron_variant	Intron 14 of 17	1	NM_015148.4	ENSP00000234040.5

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27534 AN: 152038 Hom.: 2739 Cov.: 33

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.0527

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.217

GnomAD4 exome AF: 0.212 AC: 176509 AN: 832514 Hom.: 18954 Cov.: 28 AF XY: 0.212 AC XY: 81380 AN XY: 384450

African (AFR) AF: 0.118 AC: 1855 AN: 15776

American (AMR) AF: 0.143 AC: 141 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 1281 AN: 5150

East Asian (EAS) AF: 0.0570 AC: 207 AN: 3630

South Asian (SAS) AF: 0.237 AC: 3899 AN: 16448

European-Finnish (FIN) AF: 0.207 AC: 58 AN: 280

Middle Eastern (MID) AF: 0.261 AC: 422 AN: 1618

European-Non Finnish (NFE) AF: 0.214 AC: 162945 AN: 761344

Other (OTH) AF: 0.209 AC: 5701 AN: 27284

GnomAD4 genome AF: 0.181 AC: 27538 AN: 152156 Hom.: 2735 Cov.: 33 AF XY: 0.178 AC XY: 13272 AN XY: 74366

African (AFR) AF: 0.121 AC: 5015 AN: 41504

American (AMR) AF: 0.140 AC: 2144 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 828 AN: 3472

East Asian (EAS) AF: 0.0526 AC: 273 AN: 5192

South Asian (SAS) AF: 0.244 AC: 1172 AN: 4810

European-Finnish (FIN) AF: 0.212 AC: 2241 AN: 10566

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15104 AN: 67988

Other (OTH) AF: 0.214 AC: 453 AN: 2116

Alfa AF: 0.198 Hom.: 419

Bravo AF: 0.171

Asia WGS AF: 0.143 AC: 495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.62
DANN	Benign	0.71
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

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: rs17382723; hg19: chr2-242053546;