rs767788896

Variant names:

• chr20-44651602-G-A
• rs767788896
• NM_000022.4:c.6C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-44651602-G-A
• chr20-44651602-G-C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_000022.4(ADA):​c.6C>T​(p.Ala2Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000306 in 1,537,918 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000032 (1 hom.)
• Consequence: ADA NM_000022.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.731
• Publications: 544 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 20-44651602-G-A is Benign according to our data. Variant chr20-44651602-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 536192.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.731 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADA	NM_000022.4	c.6C>T	p.Ala2Ala	synonymous_variant	Exon 1 of 12	ENST00000372874.9	NP_000013.2
ADA	NM_001322051.2	c.6C>T	p.Ala2Ala	synonymous_variant	Exon 1 of 11		NP_001308980.1
ADA	NR_136160.2	n.98C>T		non_coding_transcript_exon_variant	Exon 1 of 11
ADA	NM_001322050.2	c.-284C>T		5_prime_UTR_variant	Exon 1 of 11		NP_001308979.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADA	ENST00000372874.9	c.6C>T	p.Ala2Ala	synonymous_variant	Exon 1 of 12	1	NM_000022.4	ENSP00000361965.4
ADA	ENST00000695995.1	c.6C>T	p.Ala2Ala	synonymous_variant	Exon 1 of 9			ENSP00000512318.1
ADA	ENST00000695991.1	c.6C>T	p.Ala2Ala	synonymous_variant	Exon 1 of 8			ENSP00000512314.1
ADA	ENST00000696038.1	n.6C>T		non_coding_transcript_exon_variant	Exon 1 of 9			ENSP00000512344.1

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151582 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000418

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000102 AC: 14 AN: 137560 AF XY: 0.000131

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000186

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000317 AC: 44 AN: 1386336 Hom.: 1 Cov.: 31 AF XY: 0.0000438 AC XY: 30 AN XY: 685546

African (AFR) AF: 0.00 AC: 0 AN: 30850

American (AMR) AF: 0.00 AC: 0 AN: 36942

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25012

East Asian (EAS) AF: 0.00 AC: 0 AN: 35750

South Asian (SAS) AF: 0.000427 AC: 34 AN: 79670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34238

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4320

European-Non Finnish (NFE) AF: 0.00000832 AC: 9 AN: 1081854

Other (OTH) AF: 0.0000173 AC: 1 AN: 57700

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151582 Hom.: 1 Cov.: 32 AF XY: 0.0000405 AC XY: 3 AN XY: 74016

African (AFR) AF: 0.00 AC: 0 AN: 41258

American (AMR) AF: 0.00 AC: 0 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.000418 AC: 2 AN: 4780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10540

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67860

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Nov 30, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	14
DANN	Benign	0.97
PhyloP100		0.73
PromoterAI		-0.087	Neutral
Mutation Taster		=100/0	polymorphism

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: rs767788896; hg19: chr20-43280243;