Genetic Variant CROCC2:p.Ser818Ser (chr2-240949069-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001351305.2(CROCC2):c.2454C>T(p.Ser818Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00029 in 1,547,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 0 hom. )

Consequence

CROCC2
NM_001351305.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.04

Variant links:

Genes affected

CROCC2 (HGNC:51677): (ciliary rootlet coiled-coil, rootletin family member 2)

CROCC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 2-240949069-C-T is Benign according to our data. Variant chr2-240949069-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2652102.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.04 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CROCC2	NM_001351305.2 link	c.2454C>T	p.Ser818Ser	synonymous_variant	Exon 16 of 32	ENST00000690015.1	NP_001338234.1
CROCC2	XM_024453115.2 link	c.2454C>T	p.Ser818Ser	synonymous_variant	Exon 16 of 31		XP_024308883.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CROCC2	ENST00000690015.1 link	c.2454C>T	p.Ser818Ser	synonymous_variant	Exon 16 of 32		NM_001351305.2	ENSP00000508848.1		H7BZ55
CROCC2	ENST00000443866.2 link	c.2454C>T	p.Ser818Ser	synonymous_variant	Exon 16 of 32	5		ENSP00000397968.2		A0A8J8ZEH8

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000303

AC:

AN:

145148

Hom.:

AF XY:

0.000319

AC XY:

AN XY:

78356

show subpopulations

Gnomad AFR exome

AF:

0.000149

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000449

Gnomad FIN exome

AF:

0.000760

Gnomad NFE exome

AF:

0.000562

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000294

AC:

410

AN:

1394960

Hom.:

Cov.:

AF XY:

0.000276

AC XY:

190

AN XY:

687994

show subpopulations

Gnomad4 AFR exome

AF:

0.0000635

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.0000127

Gnomad4 FIN exome

AF:

0.000978

Gnomad4 NFE exome

AF:

0.000314

Gnomad4 OTH exome

AF:

0.000329

GnomAD4 genome

AF:

0.000250

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000942

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000473

Hom.:

Bravo

AF:

0.000151

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CROCC2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.096

DANN

Benign

0.56

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

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