Variant 21-40042597-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001389.5(DSCAM):c.5460C>T(p.His1820His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000748 in 1,614,102 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 5 hom., cov: 33)

Exomes 𝑓: 0.00047 ( 2 hom. )

Consequence

DSCAM
NM_001389.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.195

Variant links:

Genes affected

DSCAM (HGNC:3039): (DS cell adhesion molecule) This gene is a member of the immunoglobulin superfamily of cell adhesion molecules (Ig-CAMs), and is involved in human central and peripheral nervous system development. This gene is a candidate for Down syndrome and congenital heart disease (DSCHD). A gene encoding a similar Ig-CAM protein is located on chromosome 11. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2012]

DSCAM links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 21-40042597-G-A is Benign according to our data. Variant chr21-40042597-G-A is described in ClinVar as [Benign]. Clinvar id is 726823.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.195 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00337 (513/152246) while in subpopulation AFR AF= 0.0115 (478/41544). AF 95% confidence interval is 0.0107. There are 5 homozygotes in gnomad4. There are 245 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 513 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSCAM	NM_001389.5 link	c.5460C>T	p.His1820His	synonymous_variant	32/33	ENST00000400454.6	NP_001380.2	O60469-1
DSCAM	NM_001271534.3 link	c.5460C>T	p.His1820His	synonymous_variant	32/33		NP_001258463.1
DSCAM	XM_017028281.2 link	c.4752C>T	p.His1584His	synonymous_variant	29/30		XP_016883770.1
DSCAM	NR_073202.3 link	n.5766C>T		non_coding_transcript_exon_variant	32/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DSCAM	ENST00000400454.6 link	c.5460C>T	p.His1820His	synonymous_variant	32/33	1	NM_001389.5	ENSP00000383303.1	O60469-1
DSCAM	ENST00000404019.2 link	c.4716C>T	p.His1572His	synonymous_variant	28/29	1		ENSP00000385342.2	Q8WY19
DSCAM	ENST00000617870.4 link	c.4965C>T	p.His1655His	synonymous_variant	29/30	5		ENSP00000478698.1	A0A087WUI7

Frequencies

GnomAD3 genomes

AF:

0.00338

AC:

514

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0115

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00101

AC:

252

AN:

249560

Hom.:

AF XY:

0.000746

AC XY:

101

AN XY:

135392

show subpopulations

Gnomad AFR exome

AF:

0.0121

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00162

Gnomad NFE exome

AF:

0.0000971

Gnomad OTH exome

AF:

0.000825

GnomAD4 exome

AF:

0.000475

AC:

694

AN:

1461856

Hom.:

Cov.:

AF XY:

0.000406

AC XY:

295

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0128

Gnomad4 AMR exome

AF:

0.000581

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000185

Gnomad4 FIN exome

AF:

0.00154

Gnomad4 NFE exome

AF:

0.0000854

Gnomad4 OTH exome

AF:

0.000762

GnomAD4 genome

AF:

0.00337

AC:

513

AN:

152246

Hom.:

Cov.:

AF XY:

0.00329

AC XY:

245

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0115

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00186

Hom.:

Bravo

AF:

0.00391

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 13, 2018

- -

DSCAM-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 27, 2023

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

1.4

DANN

Benign

0.52

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over