2-26577573-C-G

Variant names:

• chr2-26577573-C-G
• rs775521325
• NM_001105519.3:c.406C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001105519.3(CIMIP2C):​c.406C>G​(p.Pro136Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P136S) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: CIMIP2C NM_001105519.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.80

Genes affected

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

ACMG classification

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=0.23198146).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIMIP2C	NM_001105519.3	c.406C>G	p.Pro136Ala	missense_variant	Exon 3 of 4	ENST00000329615.4	NP_001098989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM166C	ENST00000329615.4	c.406C>G	p.Pro136Ala	missense_variant	Exon 3 of 4	5	NM_001105519.3	ENSP00000332875.3
FAM166C	ENST00000409392.5	c.368C>G	p.Pro123Arg	missense_variant	Exon 4 of 5	3		ENSP00000386615.1
FAM166C	ENST00000453368.1	c.107C>G	p.Pro36Arg	missense_variant	Exon 2 of 4	3		ENSP00000395924.1
FAM166C	ENST00000479453.1	n.407C>G		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152194 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249340 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135298

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: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152194 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74342

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	15
DANN	Benign	0.59
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.9	L
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.17
Sift	Benign	0.13	T
Sift4G	Benign	0.21	T
Polyphen		0.070	B
Vest4		0.29
MutPred		0.52		Gain of sheet (P = 0.0049);
MVP		0.23
MPC		0.25
ClinPred		0.13	T
GERP RS		4.4
Varity_R		0.058
gMVP		0.075

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs775521325; hg19: chr2-26800441;