8-85464133-C-T

Variant names:

• chr8-85464133-C-T
• rs375803253
• NM_000067.3:c.34+18C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000067.3(CA2):​c.34+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,383,400 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CA2 NM_000067.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.213
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000067.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA2	NM_000067.3	MANE Select	c.34+18C>T		intron	N/A	NP_000058.1	P00918
	CA2	NM_001293675.2		c.-151+18C>T		intron	N/A	NP_001280604.1
	CA3-AS1	NR_121630.1		n.334+449G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA2	ENST00000285379.10	TSL:1 MANE Select	c.34+18C>T		intron	N/A	ENSP00000285379.4	P00918
	CA2	ENST00000960030.1		c.34+18C>T		intron	N/A	ENSP00000630089.1
	CA3-AS1	ENST00000754493.1		n.23G>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000802 AC: 1 AN: 124694 AF XY: 0.0000146

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000438

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1383400 Hom.: 0 Cov.: 31 AF XY: 0.00000293 AC XY: 2 AN XY: 682626

African (AFR) AF: 0.00 AC: 0 AN: 29630

American (AMR) AF: 0.0000569 AC: 2 AN: 35162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24752

East Asian (EAS) AF: 0.00 AC: 0 AN: 34630

South Asian (SAS) AF: 0.00 AC: 0 AN: 78070

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5640

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1074644

Other (OTH) AF: 0.00 AC: 0 AN: 57560

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.3
DANN	Benign	0.84
PhyloP100		0.21
PromoterAI		-0.032	Neutral

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: rs375803253; hg19: chr8-86376362;