20-44619854-G-C

Variant names:

• chr20-44619854-G-C
• ENST00000695956.1:c.239C>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The ENST00000695956.1(ADA):​c.239C>G​(p.Thr80Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T80K) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ADA ENST00000695956.1 missense
• Scores: Splicing: ADA: 0.1459
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0860

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 20-44619854-G-C is Benign according to our data. Variant chr20-44619854-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3643341.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADA	NM_000022.4	c.1079-7C>G		splice_region_variant, intron_variant	Intron 11 of 11	ENST00000372874.9	NP_000013.2
ADA	NM_001322051.2	c.1007-7C>G		splice_region_variant, intron_variant	Intron 10 of 10		NP_001308980.1
ADA	NM_001322050.2	c.674-7C>G		splice_region_variant, intron_variant	Intron 10 of 10		NP_001308979.1
ADA	NR_136160.2	n.1106-7C>G		splice_region_variant, intron_variant	Intron 10 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADA	ENST00000695956.1	c.239C>G	p.Thr80Arg	missense_variant	Exon 3 of 3			ENSP00000512285.1
ADA	ENST00000372874.9	c.1079-7C>G		splice_region_variant, intron_variant	Intron 11 of 11	1	NM_000022.4	ENSP00000361965.4
ADA	ENST00000695995.1	c.689-7C>G		splice_region_variant, intron_variant	Intron 8 of 8			ENSP00000512318.1
ADA	ENST00000695991.1	c.617-7C>G		splice_region_variant, intron_variant	Intron 7 of 7			ENSP00000512314.1
ADA	ENST00000696038.1	n.*1280C>G		non_coding_transcript_exon_variant	Exon 9 of 9			ENSP00000512344.1
ADA	ENST00000696038.1	n.*1280C>G		3_prime_UTR_variant	Exon 9 of 9			ENSP00000512344.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Feb 28, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	17
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.15
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.91		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.91		Position offset: -1
DS_AL_spliceai		0.33		Position offset: -7

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-43248495;