11-117762339-A-G

Variant names:

• chr11-117762339-A-G
• rs10892169
• NM_020693.4:c.511+14452T>C

Variant summary

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

The NM_020693.4(DSCAML1):​c.511+14452T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 152,002 control chromosomes in the GnomAD database, including 37,895 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 0.68 (37895 hom., cov: 31)
• Consequence: DSCAML1 NM_020693.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• Publications: 2 publications found

Genes affected

DSCAML1 (HGNC:14656): (DS cell adhesion molecule like 1) The protein encoded by this gene is a member of the Ig superfamily of cell adhesion molecules and is involved in neuronal differentiation. The encoded membrane-bound protein localizes to the cell surface, where it forms aggregates that repel neuronal processes of the same cell type. [provided by RefSeq, Sep 2016]

DSCAML1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• motor neuron disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• retinal disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• retinitis pigmentosa

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020693.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSCAML1	NM_020693.4	MANE Select	c.511+14452T>C		intron	N/A	NP_065744.3
	DSCAML1	NM_001367904.1		c.511+14452T>C		intron	N/A	NP_001354833.1
	DSCAML1	NM_001367905.1		c.103+14452T>C		intron	N/A	NP_001354834.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSCAML1	ENST00000651296.2	MANE Select	c.511+14452T>C		intron	N/A	ENSP00000498769.1
	DSCAML1	ENST00000321322.6	TSL:1	c.691+14452T>C		intron	N/A	ENSP00000315465.6
	DSCAML1	ENST00000651172.1		c.691+14452T>C		intron	N/A	ENSP00000498407.1

Frequencies

GnomAD3 genomes AF: 0.684 AC: 103894 AN: 151884 Hom.: 37881 Cov.: 31

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.841

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.707

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.698

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

GnomAD4 genome AF: 0.684 AC: 103950 AN: 152002 Hom.: 37895 Cov.: 31 AF XY: 0.691 AC XY: 51300 AN XY: 74292

African (AFR) AF: 0.409 AC: 16950 AN: 41396

American (AMR) AF: 0.799 AC: 12216 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 2640 AN: 3470

East Asian (EAS) AF: 0.841 AC: 4346 AN: 5166

South Asian (SAS) AF: 0.791 AC: 3801 AN: 4806

European-Finnish (FIN) AF: 0.819 AC: 8660 AN: 10580

Middle Eastern (MID) AF: 0.702 AC: 205 AN: 292

European-Non Finnish (NFE) AF: 0.777 AC: 52830 AN: 67972

Other (OTH) AF: 0.698 AC: 1478 AN: 2116

Alfa AF: 0.756 Hom.: 87348

Bravo AF: 0.672

Asia WGS AF: 0.760 AC: 2640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.20
DANN	Benign	0.46
PhyloP100		-1.7
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: rs10892169; hg19: chr11-117633054;