22-20319694-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_033257.4(DGCR6L):c.216C>T(p.His72=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00331 in 1,612,498 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0025 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0034 (19 hom.)
• Consequence: DGCR6L NM_033257.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.277

Genes affected

DGCR6L (HGNC:18551): (DiGeorge syndrome critical region gene 6 like) This gene, the result of a duplication at this locus, is one of two functional genes encoding nearly identical proteins that have similar expression patterns. The product of this gene is a protein that shares homology with the Drosophila gonadal protein, expressed in gonadal tissues and germ cells, and with the human laminin gamma-1 chain that functions in cell attachment and migration. This gene is located in a region of chromosome 22 implicated in the DiGeorge syndrome, one facet of a broader collection of anomalies referred to as the CATCH 22 syndrome. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007329792).
• BP6: Variant 22-20319694-G-A is Benign according to our data. Variant chr22-20319694-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 710255.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.277 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGCR6L	NM_033257.4	c.216C>T	p.His72=	synonymous_variant	2/5	ENST00000248879.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGCR6L	ENST00000248879.8	c.216C>T	p.His72=	synonymous_variant	2/5	1	NM_033257.4	P1
DGCR6L	ENST00000443409.1	c.216C>T	p.His72=	synonymous_variant, NMD_transcript_variant	2/4	1
DGCR6L	ENST00000405465.3	c.203C>T	p.Thr68Ile	missense_variant	2/4	3

Frequencies

GnomAD3 genomes AF: 0.00250 AC: 381 AN: 152238 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000796

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00222

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00416

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00262 AC: 652 AN: 248510 Hom.: 1 AF XY: 0.00266 AC XY: 359 AN XY: 134904

Gnomad AFR exome AF: 0.000691

Gnomad AMR exome AF: 0.00189

Gnomad ASJ exome AF: 0.00311

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000983

Gnomad FIN exome AF: 0.00159

Gnomad NFE exome AF: 0.00434

Gnomad OTH exome AF: 0.00364

GnomAD4 exome AF: 0.00339 AC: 4956 AN: 1460142 Hom.: 19 Cov.: 31 AF XY: 0.00344 AC XY: 2499 AN XY: 726362

Gnomad4 AFR exome AF: 0.000808

Gnomad4 AMR exome AF: 0.00202

Gnomad4 ASJ exome AF: 0.00260

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.00166

Gnomad4 NFE exome AF: 0.00402

Gnomad4 OTH exome AF: 0.00307

GnomAD4 genome AF: 0.00250 AC: 381 AN: 152356 Hom.: 0 Cov.: 34 AF XY: 0.00221 AC XY: 165 AN XY: 74502

Gnomad4 AFR AF: 0.000793

Gnomad4 AMR AF: 0.00222

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.00416

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00344 Hom.: 0

Bravo AF: 0.00261

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00349 AC: 30

ExAC AF: 0.00250 AC: 303

EpiCase AF: 0.00491

EpiControl AF: 0.00475

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Aug 13, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	DGCR6L: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.36
Cadd	Benign	8.3
Dann	Benign	0.94
DEOGEN2	Benign	0.0055	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.0073	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;N
PROVEAN	Benign	1.2	N
REVEL	Benign	0.016
Sift	Benign	0.20	T
Sift4G	Benign	0.44	T
Vest4		0.33
MVP		0.30
ClinPred		0.0090	T
GERP RS		0.91

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: rs1210827; hg19: chr22-20307217;