2-108846060-A-T

Position:

• chr2-108846060-A-T

Variant summary

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

The NM_144978.3(CCDC138):​c.1324-678A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.914 in 152,214 control chromosomes in the GnomAD database, including 63,702 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 0.91 (63702 hom., cov: 31)
• Consequence: CCDC138 NM_144978.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.458

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC138	NM_144978.3	c.1324-678A>T		intron_variant		ENST00000295124.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC138	ENST00000295124.9	c.1324-678A>T		intron_variant		2	NM_144978.3	P1
CCDC138	ENST00000412964.6	c.1324-678A>T		intron_variant		1
CCDC138	ENST00000456512.1	c.1014-678A>T		intron_variant		5
CCDC138	ENST00000409529.6	c.*1129-678A>T		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.914 AC: 139044 AN: 152094 Hom.: 63644 Cov.: 31

Gnomad AFR AF: 0.923

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.938

Gnomad ASJ AF: 0.920

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.920

Gnomad FIN AF: 0.911

Gnomad MID AF: 0.898

Gnomad NFE AF: 0.898

Gnomad OTH AF: 0.921

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

GnomAD4 genome AF: 0.914 AC: 139163 AN: 152214 Hom.: 63702 Cov.: 31 AF XY: 0.916 AC XY: 68166 AN XY: 74428

Gnomad4 AFR AF: 0.923

Gnomad4 AMR AF: 0.938

Gnomad4 ASJ AF: 0.920

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.920

Gnomad4 FIN AF: 0.911

Gnomad4 NFE AF: 0.898

Gnomad4 OTH AF: 0.922

Alfa AF: 0.903 Hom.: 7714

Bravo AF: 0.917

Asia WGS AF: 0.939 AC: 3267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.35
DANN	Benign	0.25

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: rs10496425; hg19: chr2-109462516; COSMIC: COSV54565592;