Variant chr2-26576162-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001105519.3(CIMIP2C):c.335C>T(p.Thr112Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0004 in 1,613,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00083 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00036 ( 0 hom. )

Consequence

CIMIP2C
NM_001105519.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.647

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_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.006105721).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIMIP2C	NM_001105519.3 link	c.335C>T	p.Thr112Met	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.335C>T	p.Thr112Met	missense_variant	2/4	5	NM_001105519.3	ENSP00000332875.3	A6NJV1
FAM166C	ENST00000409392.5 link	c.297C>T	p.Tyr99Tyr	synonymous_variant	3/5	3		ENSP00000386615.1	B8ZZ55
FAM166C	ENST00000453368.1 link	c.36C>T	p.Tyr12Tyr	synonymous_variant	1/4	3		ENSP00000395924.1	H7C0N2
FAM166C	ENST00000479453.1 link	n.336C>T		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

AF:

0.000828

AC:

126

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00251

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000274

AC:

AN:

248256

Hom.:

AF XY:

0.000185

AC XY:

AN XY:

134780

show subpopulations

Gnomad AFR exome

AF:

0.00213

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000266

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000356

AC:

520

AN:

1461226

Hom.:

Cov.:

AF XY:

0.000319

AC XY:

232

AN XY:

726924

show subpopulations

Gnomad4 AFR exome

AF:

0.00263

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000353

Gnomad4 OTH exome

AF:

0.000464

GnomAD4 genome

AF:

0.000827

AC:

126

AN:

152342

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00250

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000337

Hom.:

Bravo

AF:

0.000888

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00100

AC:

ESP6500EA

AF:

0.000240

AC:

ExAC

AF:

0.000281

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000178

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.335C>T (p.T112M) alteration is located in exon 2 (coding exon 2) of the C2orf70 gene. This alteration results from a C to T substitution at nucleotide position 335, causing the threonine (T) at amino acid position 112 to be replaced by a methionine (M). 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

Benign

0.079

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.63

CADD

Benign

3.3

DANN

Benign

0.90

DEOGEN2

Benign

0.0042

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.25

M_CAP

Benign

0.0027

MetaRNN

Benign

0.0061

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PROVEAN

Benign

-0.57

REVEL

Benign

0.018

Sift

Benign

0.11

Sift4G

Benign

0.11

Polyphen

0.081

Vest4

0.18

MVP

0.030

MPC

0.22

ClinPred

0.0041

GERP RS

-7.9

Varity_R

0.016

gMVP

0.20

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