Variant 21-40042669-T-G 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.5388A>C(p.Arg1796Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000779 in 1,271,104 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00075 ( 4 hom. )

Consequence

DSCAM
NM_001389.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.122

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=-0.51).

BP6

Variant 21-40042669-T-G is Benign according to our data. Variant chr21-40042669-T-G is described in ClinVar as [Benign]. Clinvar id is 742975.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.122 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00137 (77/56398) while in subpopulation SAS AF= 0.00563 (13/2310). AF 95% confidence interval is 0.00333. There are 0 homozygotes in gnomad4. There are 40 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High AC in GnomAd4 at 77 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSCAM	NM_001389.5 link	c.5388A>C	p.Arg1796Arg	synonymous_variant	32/33	ENST00000400454.6	NP_001380.2	O60469-1
DSCAM	NM_001271534.3 link	c.5388A>C	p.Arg1796Arg	synonymous_variant	32/33		NP_001258463.1
DSCAM	XM_017028281.2 link	c.4680A>C	p.Arg1560Arg	synonymous_variant	29/30		XP_016883770.1
DSCAM	NR_073202.3 link	n.5694A>C		non_coding_transcript_exon_variant	32/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DSCAM	ENST00000400454.6 link	c.5388A>C	p.Arg1796Arg	synonymous_variant	32/33	1	NM_001389.5	ENSP00000383303.1	O60469-1
DSCAM	ENST00000404019.2 link	c.4644A>C	p.Arg1548Arg	synonymous_variant	28/29	1		ENSP00000385342.2	Q8WY19
DSCAM	ENST00000617870.4 link	c.4893A>C	p.Arg1631Arg	synonymous_variant	29/30	5		ENSP00000478698.1	A0A087WUI7

Frequencies

GnomAD3 genomes

AF:

0.00139

AC:

AN:

56274

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000451

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00447

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00605

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0294

Gnomad NFE

AF:

0.00129

Gnomad OTH

AF:

0.00153

GnomAD3 exomes

AF:

0.00107

AC:

205

AN:

191766

Hom.:

AF XY:

0.00134

AC XY:

141

AN XY:

105048

show subpopulations

Gnomad AFR exome

AF:

0.0000834

Gnomad AMR exome

AF:

0.000677

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00578

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000641

Gnomad OTH exome

AF:

0.00185

GnomAD4 exome

AF:

0.000752

AC:

913

AN:

1214706

Hom.:

Cov.:

AF XY:

0.000943

AC XY:

553

AN XY:

586716

show subpopulations

Gnomad4 AFR exome

AF:

0.000407

Gnomad4 AMR exome

AF:

0.000810

Gnomad4 ASJ exome

AF:

0.0000968

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00885

Gnomad4 FIN exome

AF:

0.0000505

Gnomad4 NFE exome

AF:

0.000470

Gnomad4 OTH exome

AF:

0.00125

GnomAD4 genome

AF:

0.00137

AC:

AN:

56398

Hom.:

Cov.:

AF XY:

0.00145

AC XY:

AN XY:

27624

show subpopulations

Gnomad4 AFR

AF:

0.000446

Gnomad4 AMR

AF:

0.00446

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00563

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00129

Gnomad4 OTH

AF:

0.00149

Alfa

AF:

0.00145

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

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

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

5.2

DANN

Benign

0.69

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