rs550877583

Variant names:

• chr17-20580182-C-A
• rs550877583
• NM_001190790.2:c.299C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-20580182-C-A
• chr17-20580182-C-T

Variant summary

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

The NM_001190790.2(CDRT15L2):​c.299C>A​(p.Ala100Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A100V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDRT15L2 NM_001190790.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.705
• Publications: 1 publications found

Genes affected

CDRT15L2 (HGNC:34075): (CMT1A duplicated region transcript 15 like 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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 (MetaRNN=0.089298755).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001190790.2. 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
	CDRT15L2	NM_001190790.2	MANE Select	c.299C>A	p.Ala100Glu	missense	Exon 2 of 2	NP_001177719.1	A8MXV6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDRT15L2	ENST00000399044.1	TSL:2 MANE Select	c.299C>A	p.Ala100Glu	missense	Exon 2 of 2	ENSP00000382000.1	A8MXV6
	CDRT15L2	ENST00000661883.1		c.299C>A	p.Ala100Glu	missense	Exon 2 of 3	ENSP00000499342.1	A0A590UJC2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152090 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.55e-7 AC: 1 AN: 1325374 Hom.: 0 Cov.: 31 AF XY: 0.00000155 AC XY: 1 AN XY: 645936

African (AFR) AF: 0.0000342 AC: 1 AN: 29208

American (AMR) AF: 0.00 AC: 0 AN: 24038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20026

East Asian (EAS) AF: 0.00 AC: 0 AN: 35200

South Asian (SAS) AF: 0.00 AC: 0 AN: 66128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45970

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1044774

Other (OTH) AF: 0.00 AC: 0 AN: 54720

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152090 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74280

African (AFR) AF: 0.0000241 AC: 1 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	8.5
DANN	Benign	0.72
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0080	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.70
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.010
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.020	D
Vest4		0.071
MutPred		0.25		Gain of solvent accessibility (P = 0.08)
MVP		0.16
MPC		0.59
ClinPred		0.15	T
GERP RS		0.38
PromoterAI		-0.033	Neutral
Varity_R		0.13
gMVP		0.020
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs550877583; hg19: chr17-20483495;