17-50110520-C-T

Position:

• chr17-50110520-C-T

Variant summary

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

The NM_001257359.2(SAMD14):​c.*2373G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 155,112 control chromosomes in the GnomAD database, including 25,308 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 0.57 (24818 hom., cov: 32)
  • Exomes 𝑓: 0.54 (490 hom.)
• Consequence: SAMD14 NM_001257359.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.942

Genes affected

SAMD14 (HGNC:27312): (sterile alpha motif domain containing 14) Predicted to enable actin filament binding activity. Predicted to be involved in actin filament organization; calcium-mediated signaling; and neuron projection development. Predicted to be active in several cellular components, including actin cytoskeleton; dendrite; and postsynaptic density. [provided by Alliance of Genome Resources, Apr 2022]

PDK2 (HGNC:8810): (pyruvate dehydrogenase kinase 2) This gene encodes a member of the pyruvate dehydrogenase kinase family. The encoded protein phosphorylates pyruvate dehydrogenase, down-regulating the activity of the mitochondrial pyruvate dehydrogenase complex. Overexpression of this gene may play a role in both cancer and diabetes. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SAMD14	NM_001257359.2	c.*2373G>A		3_prime_UTR_variant	10/10	ENST00000330175.9
PDK2	NM_002611.5	c.*423C>T		3_prime_UTR_variant	11/11	ENST00000503176.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAMD14	ENST00000330175.9	c.*2373G>A		3_prime_UTR_variant	10/10	1	NM_001257359.2	P1
PDK2	ENST00000503176.6	c.*423C>T		3_prime_UTR_variant	11/11	1	NM_002611.5	P1
PDK2	ENST00000007708.7	c.*423C>T		3_prime_UTR_variant	12/12	2
PDK2	ENST00000614357.4	c.*423C>T		3_prime_UTR_variant	11/11	5

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86496 AN: 151792 Hom.: 24797 Cov.: 32

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.566

GnomAD4 exome AF: 0.541 AC: 1733 AN: 3202 Hom.: 490 Cov.: 0 AF XY: 0.525 AC XY: 914 AN XY: 1742

Gnomad4 AFR exome AF: 0.721

Gnomad4 AMR exome AF: 0.487

Gnomad4 ASJ exome AF: 0.745

Gnomad4 EAS exome AF: 0.620

Gnomad4 SAS exome AF: 0.387

Gnomad4 FIN exome AF: 0.521

Gnomad4 NFE exome AF: 0.532

Gnomad4 OTH exome AF: 0.539

GnomAD4 genome AF: 0.570 AC: 86559 AN: 151910 Hom.: 24818 Cov.: 32 AF XY: 0.567 AC XY: 42088 AN XY: 74242

Gnomad4 AFR AF: 0.644

Gnomad4 AMR AF: 0.516

Gnomad4 ASJ AF: 0.669

Gnomad4 EAS AF: 0.563

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.547

Gnomad4 OTH AF: 0.562

Alfa AF: 0.553 Hom.: 24531

Bravo AF: 0.574

Asia WGS AF: 0.514 AC: 1786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.43
DANN	Benign	0.38

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: rs1063647; hg19: chr17-48187884;