1-33012984-GCA-G

Position:

• chr1-33012984-GCA-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP6_Moderate BS1

The NM_001625.4(AK2):​c.*195_*196del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,168,730 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00031 (0 hom., cov: 32)
  • Exomes 𝑓: 0.014 (0 hom.)
• Consequence: AK2 NM_001625.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.229

Genes affected

AK2 (HGNC:362): (adenylate kinase 2) Adenylate kinases are involved in regulating the adenine nucleotide composition within a cell by catalyzing the reversible transfer of phosphate groups among adenine nucleotides. Three isozymes of adenylate kinase, namely 1, 2, and 3, have been identified in vertebrates; this gene encodes isozyme 2. Expression of these isozymes is tissue-specific and developmentally regulated. Isozyme 2 is localized in the mitochondrial intermembrane space and may play a role in apoptosis. Mutations in this gene are the cause of reticular dysgenesis. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 1 and 2.[provided by RefSeq, Nov 2010]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 1-33012984-GCA-G is Benign according to our data. Variant chr1-33012984-GCA-G is described in ClinVar as [Benign]. Clinvar id is 1232355.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000313 (47/150270) while in subpopulation SAS AF= 0.00084 (4/4764). AF 95% confidence interval is 0.000484. There are 0 homozygotes in gnomad4. There are 30 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AK2	NM_001625.4	c.*195_*196del		3_prime_UTR_variant	6/6	ENST00000672715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AK2	ENST00000672715.1	c.*195_*196del		3_prime_UTR_variant	6/6		NM_001625.4	P3
	ENST00000427524.1	n.246-18034_246-18033del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.000313 AC: 47 AN: 150170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000683

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000839

Gnomad FIN AF: 0.000491

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000149

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0137 AC: 13915 AN: 1018460 Hom.: 0 AF XY: 0.0149 AC XY: 7376 AN XY: 495884

Gnomad4 AFR exome AF: 0.0196

Gnomad4 AMR exome AF: 0.0390

Gnomad4 ASJ exome AF: 0.0264

Gnomad4 EAS exome AF: 0.0448

Gnomad4 SAS exome AF: 0.0175

Gnomad4 FIN exome AF: 0.0440

Gnomad4 NFE exome AF: 0.0102

Gnomad4 OTH exome AF: 0.0201

GnomAD4 genome AF: 0.000313 AC: 47 AN: 150270 Hom.: 0 Cov.: 32 AF XY: 0.000409 AC XY: 30 AN XY: 73384

Gnomad4 AFR AF: 0.000682

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000840

Gnomad4 FIN AF: 0.000491

Gnomad4 NFE AF: 0.000149

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 22, 2015

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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: rs368005323; hg19: chr1-33478585;