8-85477174-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000067.3(CA2):c.562T>C(p.Leu188Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 1,613,494 control chromosomes in the GnomAD database, including 293,212 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 30762 hom., cov: 30)

Exomes 𝑓: 0.60 ( 262450 hom. )

Consequence

CA2
NM_000067.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

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]

CA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 8-85477174-T-C is Benign according to our data. Variant chr8-85477174-T-C is described in ClinVar as [Benign]. Clinvar id is 254787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-85477174-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.062 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CA2	NM_000067.3 link	c.562T>C	p.Leu188Leu	synonymous_variant	Exon 6 of 7	ENST00000285379.10	NP_000058.1	P00918V9HW21
CA2	NM_001293675.2 link	c.259T>C	p.Leu87Leu	synonymous_variant	Exon 5 of 6		NP_001280604.1	V9HW21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CA2	ENST00000285379.10 link	c.562T>C	p.Leu188Leu	synonymous_variant	Exon 6 of 7	1	NM_000067.3	ENSP00000285379.4	P00918
CA2	ENST00000520127.5 link	n.*149T>C		non_coding_transcript_exon_variant	Exon 5 of 6	3		ENSP00000428443.1	E5RID5
CA2	ENST00000520127.5 link	n.*149T>C		3_prime_UTR_variant	Exon 5 of 6	3		ENSP00000428443.1	E5RID5
CA2	ENST00000522742.1 link	n.*336T>C		downstream_gene_variant		3		ENSP00000428947.1	E5RK37

Frequencies

GnomAD3 genomes

AF:

0.632

AC:

95839

AN:

151750

Hom.:

30737

Cov.:

show subpopulations

Gnomad AFR

AF:

0.710

Gnomad AMI

AF:

0.497

Gnomad AMR

AF:

0.570

Gnomad ASJ

AF:

0.577

Gnomad EAS

AF:

0.467

Gnomad SAS

AF:

0.447

Gnomad FIN

AF:

0.698

Gnomad MID

AF:

0.671

Gnomad NFE

AF:

0.617

Gnomad OTH

AF:

0.650

GnomAD3 exomes

AF:

0.586

AC:

147304

AN:

251460

Hom.:

44165

AF XY:

0.580

AC XY:

78779

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.717

Gnomad AMR exome

AF:

0.523

Gnomad ASJ exome

AF:

0.563

Gnomad EAS exome

AF:

0.485

Gnomad SAS exome

AF:

0.442

Gnomad FIN exome

AF:

0.697

Gnomad NFE exome

AF:

0.621

Gnomad OTH exome

AF:

0.604

GnomAD4 exome

AF:

0.596

AC:

871282

AN:

1461626

Hom.:

262450

Cov.:

AF XY:

0.592

AC XY:

430654

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.712

Gnomad4 AMR exome

AF:

0.527

Gnomad4 ASJ exome

AF:

0.560

Gnomad4 EAS exome

AF:

0.437

Gnomad4 SAS exome

AF:

0.448

Gnomad4 FIN exome

AF:

0.683

Gnomad4 NFE exome

AF:

0.609

Gnomad4 OTH exome

AF:

0.596

GnomAD4 genome

AF:

0.632

AC:

95912

AN:

151868

Hom.:

30762

Cov.:

AF XY:

0.629

AC XY:

46680

AN XY:

74198

show subpopulations

Gnomad4 AFR

AF:

0.710

Gnomad4 AMR

AF:

0.570

Gnomad4 ASJ

AF:

0.577

Gnomad4 EAS

AF:

0.467

Gnomad4 SAS

AF:

0.446

Gnomad4 FIN

AF:

0.698

Gnomad4 NFE

AF:

0.617

Gnomad4 OTH

AF:

0.650

Alfa

AF:

0.628

Hom.:

15994

Bravo

AF:

0.631

Asia WGS

AF:

0.456

AC:

1587

AN:

3478

EpiCase

AF:

0.623

EpiControl

AF:

0.615

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Osteopetrosis with renal tubular acidosis

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: 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

0.75

DANN

Benign

0.42

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over