chr5-156508710-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000337.6(SGCD):c.294+8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00663 in 1,505,194 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0061 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0067 ( 41 hom. )

Consequence

SGCD
NM_000337.6 splice_region, intron

Scores

Splicing: ADA: 0.00008836

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:20

Conservation

PhyloP100: 0.104

Publications

1 publications found

Variant links:

Genes affected

SGCD (HGNC:10807): (sarcoglycan delta) The protein encoded by this gene is one of the four known components of the sarcoglycan complex, which is a subcomplex of the dystrophin-glycoprotein complex (DGC). DGC forms a link between the F-actin cytoskeleton and the extracellular matrix. This protein is expressed most abundantly in skeletal and cardiac muscle. Mutations in this gene have been associated with autosomal recessive limb-girdle muscular dystrophy and dilated cardiomyopathy. Alternatively spliced transcript variants encoding distinct isoforms have been observed for this gene. [provided by RefSeq, Jul 2008]

SGCD Gene-Disease associations (from GenCC):

autosomal recessive limb-girdle muscular dystrophy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
autosomal recessive limb-girdle muscular dystrophy type 2F
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Myriad Women’s Health, Ambry Genetics
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
dilated cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
dilated cardiomyopathy 1L
Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

SGCD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 5-156508710-T-C is Benign according to our data. Variant chr5-156508710-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 36772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00612 (932/152314) while in subpopulation NFE AF = 0.00788 (536/68022). AF 95% confidence interval is 0.00733. There are 3 homozygotes in GnomAd4. There are 504 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCD	NM_000337.6 link	c.294+8T>C		splice_region_variant, intron_variant	Intron 4 of 8	ENST00000337851.9	NP_000328.2	Q92629-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SGCD	ENST00000337851.9 link	c.294+8T>C	splice_region_variant, intron_variant	Intron 4 of 8	1	NM_000337.6	ENSP00000338343.4	Q92629-2
SGCD	ENST00000435422.7 link	c.291+8T>C	splice_region_variant, intron_variant	Intron 3 of 7	1		ENSP00000403003.2	Q92629-1
SGCD	ENST00000517913.5 link	c.294+8T>C	splice_region_variant, intron_variant	Intron 6 of 9	5		ENSP00000429378.1	Q92629-3
SGCD	ENST00000524347.2 link	n.*158+8T>C	splice_region_variant, intron_variant	Intron 5 of 5	5		ENSP00000430794.1	E5RI34

Frequencies

GnomAD3 genomes

AF:

0.00612

AC:

932

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.0136

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0207

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00788

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00663

AC:

1540

AN:

232398

AF XY:

0.00674

show subpopulations

Gnomad AFR exome

AF:

0.00146

Gnomad AMR exome

AF:

0.00322

Gnomad ASJ exome

AF:

0.0116

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0182

Gnomad NFE exome

AF:

0.00758

Gnomad OTH exome

AF:

0.00898

GnomAD4 exome

AF:

0.00668

AC:

9042

AN:

1352880

Hom.:

Cov.:

AF XY:

0.00658

AC XY:

4455

AN XY:

677194

show subpopulations

African (AFR)

AF:

0.000878

AC:

AN:

30744

American (AMR)

AF:

0.00340

AC:

137

AN:

40300

Ashkenazi Jewish (ASJ)

AF:

0.0112

AC:

275

AN:

24648

East Asian (EAS)

AF:

0.0000256

AC:

AN:

39038

South Asian (SAS)

AF:

0.00223

AC:

179

AN:

80376

European-Finnish (FIN)

AF:

0.0176

AC:

934

AN:

52972

Middle Eastern (MID)

AF:

0.00402

AC:

AN:

5470

European-Non Finnish (NFE)

AF:

0.00701

AC:

7170

AN:

1022772

Other (OTH)

AF:

0.00525

AC:

297

AN:

56560

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

426

852

1277

1703

2129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

242

484

726

968

1210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00612

AC:

932

AN:

152314

Hom.:

Cov.:

AF XY:

0.00677

AC XY:

504

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.00137

AC:

AN:

41576

American (AMR)

AF:

0.00216

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0136

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00228

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0207

AC:

220

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00788

AC:

536

AN:

68022

Other (OTH)

AF:

0.00426

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

102

154

205

256

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00698

Hom.:

Bravo

AF:

0.00504

Asia WGS

AF:

0.00260

AC:

AN:

3474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:20

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:8

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 14, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 30, 2024

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

May 28, 2009

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:5

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Dec 26, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SGCD: BP4, BS2 -

Autosomal recessive limb-girdle muscular dystrophy type 2F

Benign:2

Feb 08, 2023

Genome-Nilou Lab

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiomyopathy

Benign:2

May 01, 2016

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 22, 2010

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Qualitative or quantitative defects of delta-sarcoglycan

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Limb-girdle muscular dystrophy, recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dilated cardiomyopathy 1L

Benign:1

Feb 08, 2023

Genome-Nilou Lab

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.69

PhyloP100

0.10

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000088

dbscSNV1_RF

Benign

0.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over