7-75109047-C-G

Variant names:

• chr7-75109047-C-G
• rs782613958
• NM_001003795.3:c.83C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001003795.3(GTF2IRD2B):​c.83C>G​(p.Ser28Cys) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 12)
• Consequence: GTF2IRD2B NM_001003795.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.08

Genes affected

GTF2IRD2B (HGNC:33125): (GTF2I repeat domain containing 2B) This gene encodes a glycosylated phosphoprotein with a leucine zipper motif, two helix-loop-helix motifs (I repeats) that are similar to domains found in the TFII-I family of transcription factors, one CHARLIE8 transposable element-like sequence, and a BED zinc finger. This gene lies within a region that is deleted in Williams-Beuren syndrome. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF2IRD2B	NM_001003795.3	c.83C>G	p.Ser28Cys	missense_variant	Exon 2 of 16	ENST00000472837.7	NP_001003795.1
GTF2IRD2B	NM_001368302.1	c.569C>G	p.Ser190Cys	missense_variant	Exon 2 of 16		NP_001355231.1
GTF2IRD2B	NM_001368301.1	c.83C>G	p.Ser28Cys	missense_variant	Exon 2 of 3		NP_001355230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF2IRD2B	ENST00000472837.7	c.83C>G	p.Ser28Cys	missense_variant	Exon 2 of 16	1	NM_001003795.3	ENSP00000480524.1

Frequencies

GnomAD3 genomes Cov.: 12

GnomAD3 exomes AF: 0.0000426 AC: 7 AN: 164410 Hom.: 0 AF XY: 0.0000460 AC XY: 4 AN XY: 87048

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000476

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 7

GnomAD4 genome Cov.: 12

ExAC AF: 0.0000266 AC: 3

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.83C>G (p.S28C) alteration is located in exon 2 (coding exon 1) of the GTF2IRD2B gene. This alteration results from a C to G substitution at nucleotide position 83, causing the serine (S) at amino acid position 28 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T;.;.;.
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.96	D;.;D;.
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.54	D;D;D;D
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Uncertain	2.5	M;.;.;.
PrimateAI	Uncertain	0.72	T
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		1.0	D;.;.;.
Vest4		0.67
MutPred		0.45		Loss of disorder (P = 0.0545);Loss of disorder (P = 0.0545);Loss of disorder (P = 0.0545);Loss of disorder (P = 0.0545);
MVP		0.055
ClinPred		0.56	D
GERP RS		3.0
Varity_R		0.25
gMVP		0.20

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: rs782613958; hg19: chr7-74524839;