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GeneBe

4-154236719-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001358235.2(DCHS2):c.7933T>C(p.Leu2645=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,613,906 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0077 ( 8 hom., cov: 32)
Exomes 𝑓: 0.012 ( 111 hom. )

Consequence

DCHS2
NM_001358235.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.318
Variant links:
Genes affected
DCHS2 (HGNC:23111): (dachsous cadherin-related 2) This gene encodes a large protein that contains many cadherin domains and likely functions in cell adhesion. Genome-wide association studies suggest that this gene may be important in Alzheimer's disease, compressive strength index, and appendicular lean mass. [provided by RefSeq, May 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-154236719-A-G is Benign according to our data. Variant chr4-154236719-A-G is described in ClinVar as [Benign]. Clinvar id is 3038093.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.318 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DCHS2NM_001358235.2 linkuse as main transcriptc.7933T>C p.Leu2645= synonymous_variant 20/20 ENST00000357232.10
LOC101927947XR_007058336.1 linkuse as main transcriptn.4255+29666A>G intron_variant, non_coding_transcript_variant
LOC101927947XR_007058335.1 linkuse as main transcriptn.689+29666A>G intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DCHS2ENST00000357232.10 linkuse as main transcriptc.7933T>C p.Leu2645= synonymous_variant 20/201 NM_001358235.2 P1Q6V1P9-1
ENST00000625026.1 linkuse as main transcriptn.740A>G non_coding_transcript_exon_variant 1/1
ENST00000660197.1 linkuse as main transcriptn.412+29666A>G intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00767
AC:
1167
AN:
152190
Hom.:
8
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00241
Gnomad AMI
AF:
0.00658
Gnomad AMR
AF:
0.00910
Gnomad ASJ
AF:
0.00664
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00166
Gnomad FIN
AF:
0.00848
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0114
Gnomad OTH
AF:
0.0105
GnomAD3 exomes
AF:
0.00776
AC:
1942
AN:
250260
Hom.:
11
AF XY:
0.00793
AC XY:
1072
AN XY:
135248
show subpopulations
Gnomad AFR exome
AF:
0.00191
Gnomad AMR exome
AF:
0.00646
Gnomad ASJ exome
AF:
0.00647
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00248
Gnomad FIN exome
AF:
0.00802
Gnomad NFE exome
AF:
0.0117
Gnomad OTH exome
AF:
0.00920
GnomAD4 exome
AF:
0.0115
AC:
16811
AN:
1461598
Hom.:
111
Cov.:
34
AF XY:
0.0112
AC XY:
8154
AN XY:
727102
show subpopulations
Gnomad4 AFR exome
AF:
0.00188
Gnomad4 AMR exome
AF:
0.00698
Gnomad4 ASJ exome
AF:
0.00677
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00234
Gnomad4 FIN exome
AF:
0.0100
Gnomad4 NFE exome
AF:
0.0134
Gnomad4 OTH exome
AF:
0.0108
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00766
AC:
1167
AN:
152308
Hom.:
8
Cov.:
32
AF XY:
0.00725
AC XY:
540
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.00241
Gnomad4 AMR
AF:
0.00909
Gnomad4 ASJ
AF:
0.00664
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00166
Gnomad4 FIN
AF:
0.00848
Gnomad4 NFE
AF:
0.0114
Gnomad4 OTH
AF:
0.0104
Alfa
AF:
0.00973
Hom.:
5
Bravo
AF:
0.00804
Asia WGS
AF:
0.00260
AC:
10
AN:
3478
EpiCase
AF:
0.0111
EpiControl
AF:
0.0133

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

DCHS2-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesFeb 27, 2019This 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
-0.87
Cadd
Benign
1.2
Dann
Benign
0.59

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.

Other links and lift over

dbSNP: rs111455548; hg19: chr4-155157871; API