20-44634186-G-C

Variant names:

• chr20-44634186-G-C
• rs6031682
• NM_000022.4:c.95+2041C>G

Variant summary

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

The NM_000022.4(ADA):​c.95+2041C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,168 control chromosomes in the GnomAD database, including 7,051 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 0.25 (7051 hom., cov: 33)
• Consequence: ADA NM_000022.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250
• Publications: 5 publications found

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]

ADA Gene-Disease associations (from GenCC):

• severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Myriad Women’s Health, Orphanet
• Omenn syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000022.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADA	NM_000022.4	MANE Select	c.95+2041C>G		intron	N/A	NP_000013.2
	ADA	NM_001322051.2		c.95+2041C>G		intron	N/A	NP_001308980.1
	ADA	NM_001322050.2		c.-195+2041C>G		intron	N/A	NP_001308979.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADA	ENST00000372874.9	TSL:1 MANE Select	c.95+2041C>G		intron	N/A	ENSP00000361965.4
	ADA	ENST00000537820.2	TSL:1	c.95+2041C>G		intron	N/A	ENSP00000441818.1
	ADA	ENST00000695995.1		c.95+2041C>G		intron	N/A	ENSP00000512318.1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37543 AN: 152050 Hom.: 7022 Cov.: 33

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.0510

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.188

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.247 AC: 37617 AN: 152168 Hom.: 7051 Cov.: 33 AF XY: 0.244 AC XY: 18163 AN XY: 74400

African (AFR) AF: 0.528 AC: 21903 AN: 41470

American (AMR) AF: 0.143 AC: 2190 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0510 AC: 177 AN: 3472

East Asian (EAS) AF: 0.276 AC: 1423 AN: 5160

South Asian (SAS) AF: 0.143 AC: 690 AN: 4832

European-Finnish (FIN) AF: 0.167 AC: 1767 AN: 10606

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8941 AN: 68016

Other (OTH) AF: 0.186 AC: 393 AN: 2116

Alfa AF: 0.0578 Hom.: 68

Bravo AF: 0.260

Asia WGS AF: 0.210 AC: 730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.3
DANN	Benign	0.68
PhyloP100		0.25
Mutation Taster		=99/1	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: rs6031682; hg19: chr20-43262827;