Variant chr2-26575978-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001105519.3(CIMIP2C):c.151G>T(p.Asp51Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000363 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

CIMIP2C
NM_001105519.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.21

Variant links:

Genes affected

CIMIP2C (HGNC:27938): (ciliary microtubule inner protein 2C) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

CIMIP2C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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, 0.961

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIMIP2C	NM_001105519.3 link	c.151G>T	p.Asp51Tyr	missense_variant	2/4	ENST00000329615.4	NP_001098989.1	A6NJV1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FAM166C	ENST00000329615.4 link	c.151G>T	p.Asp51Tyr	missense_variant	2/4	5	NM_001105519.3	ENSP00000332875.3	A6NJV1
FAM166C	ENST00000409392.5 link	c.113G>T	p.Gly38Val	missense_variant	3/5	3		ENSP00000386615.1	B8ZZ55
FAM166C	ENST00000479453.1 link	n.152G>T		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000802

AC:

AN:

249494

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135384

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000363

AC:

AN:

1461860

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

727238

show subpopulations

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:

0.0000450

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000826

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.151G>T (p.D51Y) alteration is located in exon 2 (coding exon 2) of the C2orf70 gene. This alteration results from a G to T substitution at nucleotide position 151, causing the aspartic acid (D) at amino acid position 51 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.17

CADD

Uncertain

DANN

Benign

0.61

DEOGEN2

Benign

0.24

Eigen

Benign

0.023

Eigen_PC

Benign

-0.0067

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.78

M_CAP

Benign

0.010

MetaRNN

Pathogenic

0.96

MetaSVM

Benign

-0.31

MutationAssessor

Uncertain

2.6

PROVEAN

Pathogenic

-6.9

REVEL

Uncertain

0.57

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.85

MutPred

0.81

Loss of ubiquitination at K47 (P = 0.0509);

MVP

0.50

MPC

0.89

ClinPred

0.96

GERP RS

3.9

Varity_R

0.59

gMVP

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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