20-44620200-G-A

Position:

• chr20-44620200-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000022.4(ADA):​c.1078+99C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0555 in 1,067,310 control chromosomes in the GnomAD database, including 2,135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.073 (547 hom., cov: 33)
  • Exomes 𝑓: 0.053 (1588 hom.)
• Consequence: ADA NM_000022.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.00400

Genes affected

ADA (HGNC:186): (adenosine deaminase) This gene encodes an enzyme that catalyzes the hydrolysis of adenosine to inosine in the purine catabolic pathway. Various mutations have been described for this gene and have been linked to human diseases related to impaired immune function such as severe combined immunodeficiency disease (SCID) which is the result of a deficiency in the ADA enzyme. In ADA-deficient individuals there is a marked depletion of T, B, and NK lymphocytes, and consequently, a lack of both humoral and cellular immunity. Conversely, elevated levels of this enzyme are associated with congenital hemolytic anemia. [provided by RefSeq, Sep 2019]

PKIG (HGNC:9019): (cAMP-dependent protein kinase inhibitor gamma) This gene encodes a member of the protein kinase inhibitor family. Studies of a similar protein in mice suggest that this protein acts as a potent competitive cAMP-dependent protein kinase inhibitor, and is a predominant form of inhibitor in various tissues. The encoded protein may be involved in osteogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ADA (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 20-44620200-G-A is Benign according to our data. Variant chr20-44620200-G-A is described in ClinVar as [Benign]. Clinvar id is 1173012.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADA	NM_000022.4	c.1078+99C>T		intron_variant		ENST00000372874.9	NP_000013.2
ADA	NM_001322051.2	c.1006+99C>T		intron_variant			NP_001308980.1
ADA	NM_001322050.2	c.673+99C>T		intron_variant			NP_001308979.1
ADA	NR_136160.2	n.1105+99C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADA	ENST00000372874.9	c.1078+99C>T		intron_variant		1	NM_000022.4	ENSP00000361965.4
ADA	ENST00000695995.1	c.688+99C>T		intron_variant				ENSP00000512318.1
ADA	ENST00000695991.1	c.616+99C>T		intron_variant				ENSP00000512314.1
ADA	ENST00000695956.1	c.232+99C>T		intron_variant				ENSP00000512285.1
ADA	ENST00000696038.1	n.*934C>T		non_coding_transcript_exon_variant	9/9			ENSP00000512344.1
ADA	ENST00000696038.1	n.*934C>T		3_prime_UTR_variant	9/9			ENSP00000512344.1

Frequencies

GnomAD3 genomes AF: 0.0728 AC: 11075 AN: 152146 Hom.: 546 Cov.: 33

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.0396

Gnomad AMR AF: 0.0562

Gnomad ASJ AF: 0.0784

Gnomad EAS AF: 0.00211

Gnomad SAS AF: 0.0615

Gnomad FIN AF: 0.0420

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0494

Gnomad OTH AF: 0.0721

GnomAD4 exome AF: 0.0526 AC: 48167 AN: 915046 Hom.: 1588 AF XY: 0.0532 AC XY: 25415 AN XY: 478098

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.0710

Gnomad4 ASJ exome AF: 0.0767

Gnomad4 EAS exome AF: 0.000537

Gnomad4 SAS exome AF: 0.0622

Gnomad4 FIN exome AF: 0.0458

Gnomad4 NFE exome AF: 0.0490

Gnomad4 OTH exome AF: 0.0610

GnomAD4 genome AF: 0.0728 AC: 11091 AN: 152264 Hom.: 547 Cov.: 33 AF XY: 0.0717 AC XY: 5339 AN XY: 74466

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.0561

Gnomad4 ASJ AF: 0.0784

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.0613

Gnomad4 FIN AF: 0.0420

Gnomad4 NFE AF: 0.0494

Gnomad4 OTH AF: 0.0718

Alfa AF: 0.0701 Hom.: 62

Bravo AF: 0.0777

Asia WGS AF: 0.0400 AC: 140 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jun 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.63

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: rs45567734; hg19: chr20-43248841;