11-117570988-T-G

Variant names:

• chr11-117570988-T-G
• rs10502226
• NM_020693.4:c.512-38466A>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.512-38466A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0154 in 152,364 control chromosomes in the GnomAD database, including 36 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 0.015 (36 hom., cov: 33)
• Consequence: DSCAML1 NM_020693.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308
• Publications: 0 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=-0.62).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0776 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.512-38466A>C		intron	N/A	NP_065744.3
	DSCAML1	NM_001367904.1		c.512-38466A>C		intron	N/A	NP_001354833.1
	DSCAML1	NM_001367905.1		c.104-38466A>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.512-38466A>C		intron	N/A	ENSP00000498769.1
	DSCAML1	ENST00000321322.6	TSL:1	c.692-38466A>C		intron	N/A	ENSP00000315465.6
	DSCAML1	ENST00000651172.1		c.692-38466A>C		intron	N/A	ENSP00000498407.1

Frequencies

GnomAD3 genomes AF: 0.0154 AC: 2345 AN: 152246 Hom.: 36 Cov.: 33

Gnomad AFR AF: 0.00437

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0169

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.0837

Gnomad SAS AF: 0.0197

Gnomad FIN AF: 0.0150

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0163

Gnomad OTH AF: 0.0124

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

GnomAD4 genome AF: 0.0154 AC: 2347 AN: 152364 Hom.: 36 Cov.: 33 AF XY: 0.0151 AC XY: 1128 AN XY: 74512

African (AFR) AF: 0.00435 AC: 181 AN: 41588

American (AMR) AF: 0.0170 AC: 260 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 57 AN: 3470

East Asian (EAS) AF: 0.0841 AC: 436 AN: 5184

South Asian (SAS) AF: 0.0197 AC: 95 AN: 4830

European-Finnish (FIN) AF: 0.0150 AC: 159 AN: 10632

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0163 AC: 1111 AN: 68030

Other (OTH) AF: 0.0123 AC: 26 AN: 2114

Alfa AF: 0.00918 Hom.: 4

Bravo AF: 0.0168

Asia WGS AF: 0.0460 AC: 161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	7.8
DANN	Benign	0.77
PhyloP100		-0.31
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: rs10502226; hg19: chr11-117441703;