2-218362876-G-A

Variant names:

• chr2-218362876-G-A
• rs138318485
• NM_198559.2:c.604G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_198559.2(CATIP):​c.604G>A​(p.Glu202Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00255 in 1,613,696 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0026 (7 hom.)
• Consequence: CATIP NM_198559.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.81
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02474609).
• BP6: Variant 2-218362876-G-A is Benign according to our data. Variant chr2-218362876-G-A is described in ClinVar as Benign. ClinVar VariationId is 3770423.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

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.604G>A	p.Glu202Lys	missense	Exon 6 of 10	NP_940961.1	Q7Z7H3
	CATIP	NM_001320865.2		c.637G>A	p.Glu213Lys	missense	Exon 6 of 10	NP_001307794.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CATIP	ENST00000289388.4	TSL:1 MANE Select	c.604G>A	p.Glu202Lys	missense	Exon 6 of 10	ENSP00000289388.3	Q7Z7H3
	CATIP	ENST00000851696.1		c.637G>A	p.Glu213Lys	missense	Exon 6 of 10	ENSP00000521755.1
	CATIP	ENST00000851694.1		c.511G>A	p.Glu171Lys	missense	Exon 5 of 9	ENSP00000521753.1

Frequencies

GnomAD3 genomes AF: 0.00171 AC: 260 AN: 152194 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00287

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00136 AC: 341 AN: 250662 AF XY: 0.00148

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.000840

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000469

Gnomad NFE exome AF: 0.00246

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00264 AC: 3852 AN: 1461384 Hom.: 7 Cov.: 31 AF XY: 0.00253 AC XY: 1842 AN XY: 727000

African (AFR) AF: 0.000239 AC: 8 AN: 33478

American (AMR) AF: 0.00110 AC: 49 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86240

European-Finnish (FIN) AF: 0.000358 AC: 19 AN: 53112

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.00326 AC: 3629 AN: 1111862

Other (OTH) AF: 0.00235 AC: 142 AN: 60384

GnomAD4 genome AF: 0.00171 AC: 260 AN: 152312 Hom.: 0 Cov.: 31 AF XY: 0.00144 AC XY: 107 AN XY: 74472

African (AFR) AF: 0.000577 AC: 24 AN: 41572

American (AMR) AF: 0.00229 AC: 35 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00287 AC: 195 AN: 68030

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00198 Hom.: 1

Bravo AF: 0.00189

TwinsUK AF: 0.00512 AC: 19

ALSPAC AF: 0.00234 AC: 9

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00279 AC: 24

ExAC AF: 0.00137 AC: 166

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00305

EpiControl AF: 0.00344

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.092	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.025	T
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.8
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.48
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.35
MVP		0.64
MPC		0.73
ClinPred		0.021	T
GERP RS		3.8
Varity_R		0.24
gMVP		0.70
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs138318485; hg19: chr2-219227599; COSMIC: COSV106089561; COSMIC: COSV106089561;