2-108791765-G-A

Position:

• chr2-108791765-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_144978.3(CCDC138):​c.357G>A​(p.Ser119=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000884 in 1,599,060 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00070 (2 hom.)
• Consequence: CCDC138 NM_144978.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0990

Genes affected

CCDC138 (HGNC:26531): (coiled-coil domain containing 138)

RANBP2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 2-108791765-G-A is Benign according to our data. Variant chr2-108791765-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2651256.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.099 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC138	NM_144978.3	c.357G>A	p.Ser119=	synonymous_variant	4/15	ENST00000295124.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC138	ENST00000295124.9	c.357G>A	p.Ser119=	synonymous_variant	4/15	2	NM_144978.3	P1

Frequencies

GnomAD3 genomes AF: 0.00263 AC: 400 AN: 152030 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00778

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00138

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000473

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.00107 AC: 263 AN: 244690 Hom.: 0 AF XY: 0.000885 AC XY: 117 AN XY: 132150

Gnomad AFR exome AF: 0.00818

Gnomad AMR exome AF: 0.000596

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000386

Gnomad SAS exome AF: 0.000493

Gnomad FIN exome AF: 0.000335

Gnomad NFE exome AF: 0.000732

Gnomad OTH exome AF: 0.000665

GnomAD4 exome AF: 0.000699 AC: 1012 AN: 1446912 Hom.: 2 Cov.: 30 AF XY: 0.000686 AC XY: 494 AN XY: 719642

Gnomad4 AFR exome AF: 0.00901

Gnomad4 AMR exome AF: 0.000753

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000178

Gnomad4 SAS exome AF: 0.000346

Gnomad4 FIN exome AF: 0.000420

Gnomad4 NFE exome AF: 0.000510

Gnomad4 OTH exome AF: 0.000986

GnomAD4 genome AF: 0.00264 AC: 401 AN: 152148 Hom.: 0 Cov.: 32 AF XY: 0.00268 AC XY: 199 AN XY: 74382

Gnomad4 AFR AF: 0.00778

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.000473

Gnomad4 NFE AF: 0.000588

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00118 Hom.: 0

Bravo AF: 0.00297

Asia WGS AF: 0.00116 AC: 4 AN: 3470

EpiCase AF: 0.000710

EpiControl AF: 0.000534

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

CCDC138: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs36034137; hg19: chr2-109408221;