2-108798557-G-T

Position:

• chr2-108798557-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_144978.3(CCDC138):​c.706G>T​(p.Val236Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CCDC138 NM_144978.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.78

Genes affected

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

RANBP2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC138	NM_144978.3	c.706G>T	p.Val236Phe	missense_variant	6/15	ENST00000295124.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC138	ENST00000295124.9	c.706G>T	p.Val236Phe	missense_variant	6/15	2	NM_144978.3	P1
CCDC138	ENST00000412964.6	c.706G>T	p.Val236Phe	missense_variant	6/14	1
CCDC138	ENST00000456512.1	c.400G>T	p.Val134Phe	missense_variant	3/9	5
CCDC138	ENST00000409529.6	c.*511G>T		3_prime_UTR_variant, NMD_transcript_variant	6/14	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 05, 2022

The c.706G>T (p.V236F) alteration is located in exon 6 (coding exon 6) of the CCDC138 gene. This alteration results from a G to T substitution at nucleotide position 706, causing the valine (V) at amino acid position 236 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	.;T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.053	D
MetaRNN	Uncertain	0.74	D;D
MetaSVM	Uncertain	0.66	D
MutationAssessor	Uncertain	2.5	M;M
MutationTaster	Benign	0.78	D;D
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Uncertain	0.51
Sift	Benign	0.12	T;T
Sift4G	Benign	0.11	T;T
Polyphen		1.0	D;P
Vest4		0.88
MutPred		0.23		Loss of loop (P = 9e-04);Loss of loop (P = 9e-04);
MVP		0.97
MPC		0.23
ClinPred		0.97	D
GERP RS		4.7
Varity_R		0.32
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-109415013;