rs2043618

Variant names:

• chr10-50247011-G-C
• rs2043618
• NM_019893.4:c.127+1473C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019893.4(ASAH2):​c.127+1473C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,030 control chromosomes in the GnomAD database, including 6,614 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 0.29 (6614 hom., cov: 31)
• Consequence: ASAH2 NM_019893.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.493
• Publications: 1 publications found

Genes affected

ASAH2 (HGNC:18860): (N-acylsphingosine amidohydrolase 2) Ceramidases (EC 3.5.1.23), such as ASAH2, catalyze hydrolysis of the N-acyl linkage of ceramide, a second messenger in a variety of cellular events, to produce sphingosine. Sphingosine exerts both mitogenic and apoptosis-inducing activities, and its phosphorylated form functions as an intra- and intercellular second messenger (see MIM 603730) (Mitsutake et al., 2001 [PubMed 11328816]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASAH2	NM_019893.4	c.127+1473C>G		intron_variant	Intron 2 of 20	ENST00000682911.1	NP_063946.2
ASAH2	NM_001143974.3	c.127+1473C>G		intron_variant	Intron 2 of 19		NP_001137446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASAH2	ENST00000682911.1	c.127+1473C>G		intron_variant	Intron 2 of 20		NM_019893.4	ENSP00000506746.1
ASAH2	ENST00000395526.9	c.127+1473C>G		intron_variant	Intron 3 of 21	1		ENSP00000378897.3
ASAH2	ENST00000329428.10	c.70+1473C>G		intron_variant	Intron 1 of 18	1		ENSP00000329886.6

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43953 AN: 151912 Hom.: 6616 Cov.: 31

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.289 AC: 43967 AN: 152030 Hom.: 6614 Cov.: 31 AF XY: 0.286 AC XY: 21237 AN XY: 74314

African (AFR) AF: 0.285 AC: 11793 AN: 41450

American (AMR) AF: 0.241 AC: 3685 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1143 AN: 3466

East Asian (EAS) AF: 0.116 AC: 600 AN: 5182

South Asian (SAS) AF: 0.241 AC: 1158 AN: 4814

European-Finnish (FIN) AF: 0.313 AC: 3307 AN: 10550

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21299 AN: 67982

Other (OTH) AF: 0.298 AC: 627 AN: 2106

Alfa AF: 0.307 Hom.: 899

Bravo AF: 0.282

Asia WGS AF: 0.197 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.8
DANN	Benign	0.66
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

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: rs2043618; hg19: chr10-52006771;