NM_005315.2:c.180G>C

Variant names:

• chr22-19150104-C-G
• rs2083820412
• NM_005315.2:c.180G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005315.2(GSC2):​c.180G>C​(p.Glu60Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000937 in 853,440 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000094 (0 hom.)
• Consequence: GSC2 NM_005315.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.339
• Publications: 0 publications found

Genes affected

GSC2 (HGNC:4613): (goosecoid homeobox 2) Goosecoidlike (GSCL), a homeodomain-containing gene, resides in the critical region for VCFS/DGS on 22q11. Velocardiofacial syndrome (VCFS) is a developmental disorder characterized by conotruncal heart defects, craniofacial anomalies, and learning disabilities. VCFS is phenotypically related to DiGeorge syndrome (DGS) and both syndromes are associated with hemizygous 22q11 deletions. Because many of the tissues and structures affected in VCFS/DGS derive from the pharyngeal arches of the developing embryo, it is believed that haploinsufficiency of a gene involved in embryonic development may be responsible for its etiology. The gene is expressed in a limited number of adult tissues, as well as in early human development. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.089963764).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005315.2. 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
	GSC2	NM_005315.2	MANE Select	c.180G>C	p.Glu60Asp	missense	Exon 1 of 3	NP_005306.1	O15499

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSC2	ENST00000086933.3	TSL:5 MANE Select	c.180G>C	p.Glu60Asp	missense	Exon 1 of 3	ENSP00000086933.2	O15499

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000937 AC: 8 AN: 853440 Hom.: 0 Cov.: 22 AF XY: 0.0000101 AC XY: 4 AN XY: 396972

African (AFR) AF: 0.000434 AC: 7 AN: 16134

American (AMR) AF: 0.00 AC: 0 AN: 1796

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5752

East Asian (EAS) AF: 0.00 AC: 0 AN: 5300

South Asian (SAS) AF: 0.00 AC: 0 AN: 17384

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1730

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 773298

Other (OTH) AF: 0.0000348 AC: 1 AN: 28712

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	0.32
DANN	Benign	0.84
DEOGEN2	Benign	0.040	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.31	T
M_CAP	Pathogenic	0.63	D
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.46	N
PhyloP100		-0.34
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.12
Sift	Benign	0.30	T
Sift4G	Benign	0.60	T
Polyphen		0.0020	B
Vest4		0.099
MutPred		0.22		Loss of glycosylation at P59 (P = 0.1337)
MVP		0.14
MPC		0.39
ClinPred		0.053	T
GERP RS		-1.4
PromoterAI		-0.032	Neutral
Varity_R		0.045
gMVP		0.25
Mutation Taster		=98/2	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: rs2083820412; hg19: chr22-19137617;