2-218357133-T-G

Variant names:

• chr2-218357133-T-G
• rs202093757
• NM_198559.2:c.64T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198559.2(CATIP):​c.64T>G​(p.Cys22Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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. C22S) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: CATIP NM_198559.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400
• Publications: 0 publications found

Genes affected

CATIP (HGNC:25062): (ciliogenesis associated TTC17 interacting protein) Involved in actin filament polymerization and cilium organization. Located in several cellular components, including actin cytoskeleton; nucleus; and plasma membrane. Implicated in spermatogenic failure. [provided by Alliance of Genome Resources, Apr 2022]

CATIP-AS2 (HGNC:41079): (CATIP antisense RNA 2)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.028579682).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198559.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CATIP	NM_198559.2	MANE Select	c.64T>G	p.Cys22Gly	missense	Exon 2 of 10	NP_940961.1	Q7Z7H3
	CATIP	NM_001320865.2		c.97T>G	p.Cys33Gly	missense	Exon 2 of 10	NP_001307794.1
	CATIP-AS2	NR_125777.1		n.53+781A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CATIP	ENST00000289388.4	TSL:1 MANE Select	c.64T>G	p.Cys22Gly	missense	Exon 2 of 10	ENSP00000289388.3	Q7Z7H3
	CATIP	ENST00000851696.1		c.97T>G	p.Cys33Gly	missense	Exon 2 of 10	ENSP00000521755.1
	CATIP	ENST00000851695.1		c.97T>G	p.Cys33Gly	missense	Exon 2 of 9	ENSP00000521754.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151914 Hom.: 0 Cov.: 31

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

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151914 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74160

African (AFR) AF: 0.00 AC: 0 AN: 41358

American (AMR) AF: 0.00 AC: 0 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67976

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.7
DANN	Benign	0.55
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.2	N
PhyloP100		-0.040
PROVEAN	Benign	0.28	N
REVEL	Benign	0.017
Sift	Benign	0.57	T
Sift4G	Benign	0.41	T
Polyphen		0.0	B
Vest4		0.058
MutPred		0.18		Gain of relative solvent accessibility (P = 0.0027)
MVP		0.12
MPC		0.30
ClinPred		0.036	T
GERP RS		-2.3
PromoterAI		-0.0044	Neutral
Varity_R		0.030
gMVP		0.19
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs202093757; hg19: chr2-219221856;