17-14236785-C-A

Variant names:

• chr17-14236785-C-A
• rs759980858
• ENST00000431716.2:c.-26G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001348781.2(CDRT15):​c.-26G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDRT15 NM_001348781.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.584
• Publications: 1 publications found

Genes affected

CDRT15 (HGNC:14395): (CMT1A duplicated region transcript 15)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.0981221).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348781.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDRT15	NM_001007530.3	MANE Select	c.49G>T	p.Gly17*	stop_gained	Exon 1 of 3	NP_001007531.1	Q96T59
	CDRT15	NM_001348781.2		c.-26G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_001335710.1	F2Z3C1
	CDRT15	NM_001348781.2		c.-26G>T		5_prime_UTR	Exon 1 of 3	NP_001335710.1	F2Z3C1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDRT15	ENST00000431716.2	TSL:1	c.-26G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000399575.2	F2Z3C1
	CDRT15	ENST00000420162.7	TSL:1 MANE Select	c.49G>T	p.Gly17*	stop_gained	Exon 1 of 3	ENSP00000402355.3	Q96T59
	CDRT15	ENST00000431716.2	TSL:1	c.-26G>T		5_prime_UTR	Exon 1 of 3	ENSP00000399575.2	F2Z3C1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000128 AC: 3 AN: 234746 AF XY: 0.0000157

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000206 AC: 3 AN: 1458960 Hom.: 0 Cov.: 73 AF XY: 0.00000413 AC XY: 3 AN XY: 725772

African (AFR) AF: 0.00 AC: 0 AN: 33380

American (AMR) AF: 0.00 AC: 0 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26030

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000349 AC: 3 AN: 86054

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4208

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111420

Other (OTH) AF: 0.00 AC: 0 AN: 60170

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	23
DANN	Benign	0.96
Eigen	Benign	-0.0013
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.0047	N
PhyloP100		-0.58
Vest4		0.017
GERP RS		-1.4
PromoterAI		0.0020	Neutral
Mutation Taster		=182/18	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs759980858; hg19: chr17-14140102; COSMIC: COSV101415145;