17-79779371-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_005189.3(CBX2):​c.126C>T​(p.Ser42Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000303 in 1,613,836 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00096 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00023 ( 2 hom. )

Consequence

CBX2
NM_005189.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.52
Variant links:
Genes affected
CBX2 (HGNC:1552): (chromobox 2) This gene encodes a component of the polycomb multiprotein complex, which is required to maintain the transcriptionally repressive state of many genes throughout development via chromatin remodeling and modification of histones. Disruption of this gene in mice results in male-to-female gonadal sex reversal. Mutations in this gene are also associated with gonadal dysgenesis in humans. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Mar 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
Variant 17-79779371-C-T is Benign according to our data. Variant chr17-79779371-C-T is described in ClinVar as [Benign]. Clinvar id is 3630388.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-79779371-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=2.52 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 2 SD gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CBX2NM_005189.3 linkc.126C>T p.Ser42Ser synonymous_variant Exon 3 of 5 ENST00000310942.9 NP_005180.1 Q14781-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CBX2ENST00000310942.9 linkc.126C>T p.Ser42Ser synonymous_variant Exon 3 of 5 1 NM_005189.3 ENSP00000308750.4 Q14781-1
CBX2ENST00000269399.5 linkc.126C>T p.Ser42Ser synonymous_variant Exon 3 of 4 1 ENSP00000269399.5 Q14781-2
CBX2ENST00000571484.1 linkn.199C>T non_coding_transcript_exon_variant Exon 3 of 3 1

Frequencies

GnomAD3 genomes
AF:
0.000940
AC:
143
AN:
152206
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00234
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00222
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000532
AC:
133
AN:
250048
Hom.:
1
AF XY:
0.000435
AC XY:
59
AN XY:
135522
show subpopulations
Gnomad AFR exome
AF:
0.00242
Gnomad AMR exome
AF:
0.00136
Gnomad ASJ exome
AF:
0.00140
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000204
Gnomad OTH exome
AF:
0.00147
GnomAD4 exome
AF:
0.000235
AC:
343
AN:
1461512
Hom.:
2
Cov.:
31
AF XY:
0.000215
AC XY:
156
AN XY:
727058
show subpopulations
Gnomad4 AFR exome
AF:
0.00281
Gnomad4 AMR exome
AF:
0.00136
Gnomad4 ASJ exome
AF:
0.00138
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000863
Gnomad4 OTH exome
AF:
0.000712
GnomAD4 genome
AF:
0.000958
AC:
146
AN:
152324
Hom.:
0
Cov.:
33
AF XY:
0.000994
AC XY:
74
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.00241
Gnomad4 AMR
AF:
0.00222
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.000639
Hom.:
0
Bravo
AF:
0.00108
EpiCase
AF:
0.000382
EpiControl
AF:
0.000296

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Sep 04, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.36
CADD
Benign
15
DANN
Benign
0.93

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.

Other links and lift over

dbSNP: rs114269401; hg19: chr17-77753170; API