NM_001625.4:c.*195_*196delTG

Variant names:

• chr1-33012984-GCA-G
• rs368005323
• NM_001625.4:c.*195_*196delTG

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_*196delTG 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]

ENSG00000236065 (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 rank	MANE	Protein	UniProt
AK2	NM_001625.4	c.*195_*196delTG		3_prime_UTR_variant	Exon 6 of 6	ENST00000672715.1	NP_001616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AK2	ENST00000672715	c.*195_*196delTG		3_prime_UTR_variant	Exon 6 of 6		NM_001625.4	ENSP00000499935.1

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

Jul 22, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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;