rs6823054

Positions:

• chr4-154276677-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001358235.2(DCHS2):​c.6464-6664G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,178 control chromosomes in the GnomAD database, including 3,831 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 0.13 (3831 hom., cov: 33)
• Consequence: DCHS2 NM_001358235.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36

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]

ENSG00000280241 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCHS2	NM_001358235.2	c.6464-6664G>A		intron_variant		ENST00000357232.10	NP_001345164.1
LOC101927947	XR_007058336.1	n.4669+4391C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCHS2	ENST00000357232.10	c.6464-6664G>A		intron_variant		1	NM_001358235.2	ENSP00000349768.5

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19018 AN: 152060 Hom.: 3809 Cov.: 33

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0466

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0381

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.00348

Gnomad OTH AF: 0.0985

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

GnomAD4 genome AF: 0.125 AC: 19087 AN: 152178 Hom.: 3831 Cov.: 33 AF XY: 0.122 AC XY: 9040 AN XY: 74402

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.0464

Gnomad4 ASJ AF: 0.0458

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0379

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00348

Gnomad4 OTH AF: 0.0974

Alfa AF: 0.0750 Hom.: 279

Bravo AF: 0.143

Asia WGS AF: 0.0450 AC: 159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.21
DANN	Benign	0.54

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

Other links and lift over

dbSNP: rs6823054; hg19: chr4-155197829;