rs703

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000067.3(CA2):​c.562T>A​(p.Leu188Met) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L188L) has been classified as Benign.

Frequency

Genomes: not found (cov: 30)

Consequence

CA2
NM_000067.3 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0620
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.25546736).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CA2NM_000067.3 linkuse as main transcriptc.562T>A p.Leu188Met missense_variant 6/7 ENST00000285379.10 NP_000058.1
CA2NM_001293675.2 linkuse as main transcriptc.259T>A p.Leu87Met missense_variant 5/6 NP_001280604.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CA2ENST00000285379.10 linkuse as main transcriptc.562T>A p.Leu188Met missense_variant 6/71 NM_000067.3 ENSP00000285379 P1
CA2ENST00000520127.5 linkuse as main transcriptc.*149T>A 3_prime_UTR_variant, NMD_transcript_variant 5/63 ENSP00000428443
CA2ENST00000522742.1 linkuse as main transcript downstream_gene_variant 3 ENSP00000428947

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
Cov.:
47
GnomAD4 genome
Cov.:
30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
9.8
DANN
Benign
0.96
DEOGEN2
Benign
0.22
T
Eigen
Benign
-0.77
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.70
T
M_CAP
Benign
0.052
D
MetaRNN
Benign
0.26
T
MetaSVM
Benign
-0.54
T
MutationAssessor
Uncertain
2.7
M
MutationTaster
Benign
0.97
N
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-0.79
N
REVEL
Benign
0.23
Sift
Benign
0.19
T
Sift4G
Benign
0.22
T
Polyphen
0.76
P
Vest4
0.28
MutPred
0.47
Loss of catalytic residue at L188 (P = 0.0648);
MVP
0.69
MPC
0.58
ClinPred
0.42
T
GERP RS
-6.0
Varity_R
0.49
gMVP
0.50

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs703; hg19: chr8-86389403; API