rs149548848

Variant names:

• chr4-154235446-G-A
• rs149548848
• NM_001358235.2:c.9206C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-154235446-G-A
• chr4-154235446-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001358235.2(DCHS2):​c.9206C>T​(p.Pro3069Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000978 in 1,613,990 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00095 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00098 (14 hom.)
• Consequence: DCHS2 NM_001358235.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 3.07
• Publications: 11 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004939884).
• BP6: Variant 4-154235446-G-A is Benign according to our data. Variant chr4-154235446-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3038479.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 14 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.9206C>T	p.Pro3069Leu	missense	Exon 20 of 20	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.9206C>T	p.Pro3069Leu	missense	Exon 20 of 20	ENSP00000349768.5	Q6V1P9-1
	DCHS2	ENST00000623607.4	TSL:1	n.7840C>T		non_coding_transcript_exon	Exon 25 of 25
	ENSG00000280241	ENST00000623325.1	TSL:5	n.98+28393G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000953 AC: 145 AN: 152080 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000706

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00149 AC: 374 AN: 250564 AF XY: 0.00148

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00182

Gnomad ASJ exome AF: 0.0182

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000840

Gnomad OTH exome AF: 0.00344

GnomAD4 exome AF: 0.000981 AC: 1434 AN: 1461792 Hom.: 14 Cov.: 34 AF XY: 0.00101 AC XY: 732 AN XY: 727200

African (AFR) AF: 0.000418 AC: 14 AN: 33476

American (AMR) AF: 0.00170 AC: 76 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0186 AC: 487 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39688

South Asian (SAS) AF: 0.000325 AC: 28 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00902 AC: 52 AN: 5764

European-Non Finnish (NFE) AF: 0.000555 AC: 617 AN: 1111952

Other (OTH) AF: 0.00263 AC: 159 AN: 60394

GnomAD4 genome AF: 0.000953 AC: 145 AN: 152198 Hom.: 0 Cov.: 32 AF XY: 0.000820 AC XY: 61 AN XY: 74418

African (AFR) AF: 0.000193 AC: 8 AN: 41530

American (AMR) AF: 0.00118 AC: 18 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 57 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000706 AC: 48 AN: 68018

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00146 Hom.: 5

Bravo AF: 0.00117

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00140 AC: 12

ExAC AF: 0.00137 AC: 166

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00142

EpiControl AF: 0.000889

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	DCHS2-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Benign	0.96
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.69	D
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.0049	T
MetaSVM	Benign	-0.90	T
PhyloP100		3.1
PrimateAI	Benign	0.36	T
REVEL	Benign	0.21
MPC		0.39
ClinPred		0.045	T
GERP RS		5.8
gMVP		0.41
Mutation Taster		=68/32	polymorphism

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: rs149548848; hg19: chr4-155156598; COSMIC: COSV61768122; COSMIC: COSV61768122;