10-277559-T-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_014974.3(DIP2C):c.4437A>C(p.Thr1479=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00321 in 1,614,046 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (19 hom.)
• Consequence: DIP2C NM_014974.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.133

Genes affected

DIP2C (HGNC:29150): (disco interacting protein 2 homolog C) This gene encodes a member of the disco-interacting protein homolog 2 family. The protein shares strong similarity with a Drosophila protein which interacts with the transcription factor disco and is expressed in the nervous system. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 10-277559-T-G is Benign according to our data. Variant chr10-277559-T-G is described in ClinVar as [Benign]. Clinvar id is 771172.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.133 with no splicing effect.
• BS2: High AC in GnomAd at 419 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DIP2C	NM_014974.3	c.4437A>C	p.Thr1479=	synonymous_variant	37/37	ENST00000280886.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DIP2C	ENST00000280886.12	c.4437A>C	p.Thr1479=	synonymous_variant	37/37	1	NM_014974.3	P1
DIP2C	ENST00000634311.1	c.4635A>C	p.Thr1545=	synonymous_variant	39/39	5

Frequencies

GnomAD3 genomes AF: 0.00275 AC: 419 AN: 152182 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00215

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.0207

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00312

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00307 AC: 768 AN: 250128 Hom.: 5 AF XY: 0.00297 AC XY: 402 AN XY: 135300

Gnomad AFR exome AF: 0.00149

Gnomad AMR exome AF: 0.00203

Gnomad ASJ exome AF: 0.0246

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000687

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00326

Gnomad OTH exome AF: 0.00589

GnomAD4 exome AF: 0.00326 AC: 4759 AN: 1461746 Hom.: 19 Cov.: 32 AF XY: 0.00321 AC XY: 2334 AN XY: 727164

Gnomad4 AFR exome AF: 0.00245

Gnomad4 AMR exome AF: 0.00230

Gnomad4 ASJ exome AF: 0.0251

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000974

Gnomad4 FIN exome AF: 0.000206

Gnomad4 NFE exome AF: 0.00304

Gnomad4 OTH exome AF: 0.00611

GnomAD4 genome AF: 0.00274 AC: 418 AN: 152300 Hom.: 0 Cov.: 32 AF XY: 0.00232 AC XY: 173 AN XY: 74462

Gnomad4 AFR AF: 0.00214

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.0207

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00312

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00503 Hom.: 2

Bravo AF: 0.00313

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00387

EpiControl AF: 0.00397

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	0.28
Dann	Benign	0.67

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: rs144199668; hg19: chr10-323499;