2-168709674-G-C

Variant names:

• chr2-168709674-G-C
• rs1424937
• NM_203463.3:c.610-5327G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B.

Score: -2 - Likely Benign

-2

PM2BP4_Strong

The NM_203463.3(CERS6):​c.610-5327G>C variant causes a intron 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: 32)
• Consequence: CERS6 NM_203463.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• Publications: 0 publications found

Genes affected

CERS6 (HGNC:23826): (ceramide synthase 6) Enables sphingosine N-acyltransferase activity. Involved in ceramide biosynthetic process. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERS6	NM_203463.3	c.610-5327G>C		intron_variant	Intron 6 of 9	ENST00000305747.11	NP_982288.1
CERS6	NM_001256126.2	c.610-5327G>C		intron_variant	Intron 6 of 10		NP_001243055.1
CERS6	XM_017003749.3	c.187-5327G>C		intron_variant	Intron 3 of 7		XP_016859238.1
CERS6	XM_005246440.6	c.34-5327G>C		intron_variant	Intron 3 of 7		XP_005246497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERS6	ENST00000305747.11	c.610-5327G>C		intron_variant	Intron 6 of 9	2	NM_203463.3	ENSP00000306579.6
CERS6	ENST00000392687.4	c.610-5327G>C		intron_variant	Intron 6 of 10	1		ENSP00000376453.4

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.2
DANN	Benign	0.67
PhyloP100		0.085

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: rs1424937; hg19: chr2-169566184;