chr22-18910208-C-T

Position:

• chr22-18910208-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005675.6(DGCR6):​c.308C>T​(p.Ala103Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 0)
• Consequence: DGCR6 NM_005675.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.02

Genes affected

DGCR6 (HGNC:2846): (DiGeorge syndrome critical region gene 6) DiGeorge syndrome, and more widely, the CATCH 22 syndrome, are associated with microdeletions in chromosomal region 22q11.2. The product of this gene shares homology with the Drosophila melanogaster gonadal protein, which participates in gonadal and germ cell development, and with the gamma-1 subunit of human laminin. This gene is a candidate for involvement in DiGeorge syndrome pathology and in schizophrenia. [provided by RefSeq, Nov 2008]

ENSG00000283809 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.23551431).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGCR6	NM_005675.6	c.308C>T	p.Ala103Val	missense_variant	3/5	ENST00000331444.12	NP_005666.2
DGCR6	XM_047441509.1	c.427C>T	p.Pro143Ser	missense_variant	4/4		XP_047297465.1
DGCR6	XM_047441510.1	c.101C>T	p.Ala34Val	missense_variant	3/5		XP_047297466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGCR6	ENST00000331444.12	c.308C>T	p.Ala103Val	missense_variant	3/5	1	NM_005675.6	ENSP00000331681.6
ENSG00000283809	ENST00000638240.1	c.308C>T	p.Ala103Val	missense_variant	3/6	5		ENSP00000492446.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2024

The c.308C>T (p.A103V) alteration is located in exon 3 (coding exon 3) of the DGCR6 gene. This alteration results from a C to T substitution at nucleotide position 308, causing the alanine (A) at amino acid position 103 to be replaced by a valine (V). 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	Benign	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	T;.
Eigen	Benign	-0.067
Eigen_PC	Benign	0.078
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.78	.;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.55	N;.
REVEL	Benign	0.086
Sift	Benign	0.29	T;.
Sift4G	Benign	0.83	T;.
Polyphen		0.0050	B;.
Vest4		0.42
MutPred		0.56		Gain of MoRF binding (P = 0.0905);Gain of MoRF binding (P = 0.0905);
MVP		0.61
MPC		0.10
ClinPred		0.76	D
GERP RS		4.1
Varity_R		0.21
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-18897721;