8-85464097-G-T

Variant names:

• chr8-85464097-G-T
• NM_000067.3:c.16G>T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_000067.3(CA2):​c.16G>T​(p.Gly6Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000000716 in 1,395,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CA2 NM_000067.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.49

Genes affected

CA2 (HGNC:1373): (carbonic anhydrase 2) The protein encoded by this gene is one of several isozymes of carbonic anhydrase, which catalyzes reversible hydration of carbon dioxide. Defects in this enzyme are associated with osteopetrosis and renal tubular acidosis. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2014]

CA3-AS1 (HGNC:51657): (CA3 antisense RNA 1)

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.941

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CA2	NM_000067.3	c.16G>T	p.Gly6Trp	missense_variant	Exon 1 of 7	ENST00000285379.10	NP_000058.1
CA2	NM_001293675.2	c.-169G>T		5_prime_UTR_variant	Exon 1 of 6		NP_001280604.1
CA3-AS1	NR_121630.1	n.334+485C>A		intron_variant	Intron 1 of 2
CA3-AS1	NR_121631.1	n.106+131C>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CA2	ENST00000285379.10	c.16G>T	p.Gly6Trp	missense_variant	Exon 1 of 7	1	NM_000067.3	ENSP00000285379.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1395830 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 689626

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.25e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.85	D
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.94	D
M_CAP	Pathogenic	0.91	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Pathogenic	4.5	H
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-6.4	D
REVEL	Pathogenic	0.85
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.61
MVP		0.95
MPC		1.0
ClinPred		1.0	D
GERP RS		4.5
Varity_R		0.99
gMVP		0.89

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-86376326;