2-108872909-A-G

Position:

• chr2-108872909-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144978.3(CCDC138):​c.1694-542A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 152,070 control chromosomes in the GnomAD database, including 43,121 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.73 (43121 hom., cov: 31)
• Consequence: CCDC138 NM_144978.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

Genes affected

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

RANBP2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC138	NM_144978.3	c.1694-542A>G		intron_variant		ENST00000295124.9	NP_659415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC138	ENST00000295124.9	c.1694-542A>G		intron_variant		2	NM_144978.3	ENSP00000295124	P1
CCDC138	ENST00000412964.6	c.1694-3179A>G		intron_variant		1		ENSP00000411800
CCDC138	ENST00000608781.1	c.44-9762A>G		intron_variant		3		ENSP00000477316
CCDC138	ENST00000409529.6	c.*1499-3179A>G		intron_variant, NMD_transcript_variant		2		ENSP00000386418

Frequencies

GnomAD3 genomes AF: 0.729 AC: 110788 AN: 151952 Hom.: 43113 Cov.: 31

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.777

Gnomad AMR AF: 0.832

Gnomad ASJ AF: 0.882

Gnomad EAS AF: 0.949

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.893

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.834

Gnomad OTH AF: 0.776

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.729 AC: 110823 AN: 152070 Hom.: 43121 Cov.: 31 AF XY: 0.735 AC XY: 54635 AN XY: 74368

Gnomad4 AFR AF: 0.430

Gnomad4 AMR AF: 0.833

Gnomad4 ASJ AF: 0.882

Gnomad4 EAS AF: 0.949

Gnomad4 SAS AF: 0.750

Gnomad4 FIN AF: 0.893

Gnomad4 NFE AF: 0.834

Gnomad4 OTH AF: 0.779

Alfa AF: 0.715 Hom.: 2508

Bravo AF: 0.715

Asia WGS AF: 0.788 AC: 2741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.75
DANN	Benign	0.57

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

Other links and lift over

dbSNP: rs1073893; hg19: chr2-109489365;