chr4-154242632-TCA-T

Variant names:

• chr4-154242632-TCA-T
• rs138768083
• NM_001358235.2:c.7072+8_7072+9delTG

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_001358235.2(DCHS2):​c.7072+8_7072+9delTG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0243 in 1,604,156 control chromosomes in the GnomAD database, including 580 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.020 (48 hom., cov: 32)
  • Exomes 𝑓: 0.025 (532 hom.)
• Consequence: DCHS2 NM_001358235.2 splice_region, intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 3.33
• Publications: 0 publications found

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:58900):

LOC101927947 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP6: Variant 4-154242632-TCA-T is Benign according to our data. Variant chr4-154242632-TCA-T is described in ClinVar as Benign. ClinVar VariationId is 3037465.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0201 (3067/152250) while in subpopulation NFE AF = 0.0326 (2220/68004). AF 95% confidence interval is 0.0315. There are 48 homozygotes in GnomAd4. There are 1372 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 48 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001358235.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCHS2	NM_001358235.2	MANE Select	c.7072+8_7072+9delTG		splice_region intron	N/A	NP_001345164.1	Q6V1P9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCHS2	ENST00000357232.10	TSL:1 MANE Select	c.7072+8_7072+9delTG		splice_region intron	N/A	ENSP00000349768.5	Q6V1P9-1
	DCHS2	ENST00000623607.4	TSL:1	n.5706+8_5706+9delTG		splice_region intron	N/A
	ENSG00000280241	ENST00000623325.1	TSL:5	n.99-26429_99-26428delCA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0202 AC: 3069 AN: 152132 Hom.: 48 Cov.: 32

Gnomad AFR AF: 0.00476

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0187

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.0155

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0327

Gnomad OTH AF: 0.0249

GnomAD2 exomes AF: 0.0186 AC: 4467 AN: 239960 AF XY: 0.0191

Gnomad AFR exome AF: 0.00411

Gnomad AMR exome AF: 0.0102

Gnomad ASJ exome AF: 0.0284

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0181

Gnomad NFE exome AF: 0.0290

Gnomad OTH exome AF: 0.0198

GnomAD4 exome AF: 0.0247 AC: 35888 AN: 1451906 Hom.: 532 AF XY: 0.0244 AC XY: 17612 AN XY: 721984

African (AFR) AF: 0.00356 AC: 117 AN: 32882

American (AMR) AF: 0.0109 AC: 460 AN: 42140

Ashkenazi Jewish (ASJ) AF: 0.0278 AC: 711 AN: 25550

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39520

South Asian (SAS) AF: 0.00500 AC: 420 AN: 84040

European-Finnish (FIN) AF: 0.0168 AC: 892 AN: 53240

Middle Eastern (MID) AF: 0.0186 AC: 106 AN: 5694

European-Non Finnish (NFE) AF: 0.0287 AC: 31826 AN: 1108862

Other (OTH) AF: 0.0226 AC: 1355 AN: 59978

GnomAD4 genome AF: 0.0201 AC: 3067 AN: 152250 Hom.: 48 Cov.: 32 AF XY: 0.0184 AC XY: 1372 AN XY: 74442

African (AFR) AF: 0.00474 AC: 197 AN: 41552

American (AMR) AF: 0.0186 AC: 285 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0288 AC: 100 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00497 AC: 24 AN: 4826

European-Finnish (FIN) AF: 0.0155 AC: 165 AN: 10616

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0326 AC: 2220 AN: 68004

Other (OTH) AF: 0.0246 AC: 52 AN: 2112

Alfa AF: 0.0292 Hom.: 11

Bravo AF: 0.0193

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DCHS2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.3
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: rs138768083; hg19: chr4-155163784; COSMIC: COSV61768227;