chr10-80351984-T-C

Position:

• chr10-80351984-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001269053.2(DYDC1):​c.166A>G​(p.Lys56Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DYDC1 NM_001269053.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.45

Genes affected

DYDC1 (HGNC:23460): (DPY30 domain containing 1) This gene encodes a member of a family of proteins that contains a DPY30 domain. The encoded protein is involved in acrosome formation during spermatid development. This gene locus overlaps with a closely related gene on the opposite strand. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

DYDC2 (HGNC:23468): (DPY30 domain containing 2) This gene encodes a member of a family of proteins that contains a DPY30 domain. This gene locus overlaps with a closely related gene on the opposite strand. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

DYDC2 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03008306).
• BP6: Variant 10-80351984-T-C is Benign according to our data. Variant chr10-80351984-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2293226.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYDC1	NM_001269053.2	c.166A>G	p.Lys56Glu	missense_variant	3/7	ENST00000372202.6	NP_001255982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYDC1	ENST00000372202.6	c.166A>G	p.Lys56Glu	missense_variant	3/7	3	NM_001269053.2	ENSP00000361276.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 31, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.046
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.034
DANN	Benign	0.46
DEOGEN2	Benign	0.013	T;T;T;T;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0027	N
LIST_S2	Benign	0.098	.;T;.;T;T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.030	T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.4	N;N;N;.;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	1.1	N;N;N;N;N
REVEL	Benign	0.074
Sift	Benign	1.0	T;T;T;T;T
Sift4G	Benign	0.79	T;T;T;.;T
Polyphen		0.0	B;B;B;.;.
Vest4		0.047
MutPred		0.28		Loss of ubiquitination at K56 (P = 0.0056);Loss of ubiquitination at K56 (P = 0.0056);Loss of ubiquitination at K56 (P = 0.0056);Loss of ubiquitination at K56 (P = 0.0056);Loss of ubiquitination at K56 (P = 0.0056);
MVP		0.18
MPC		0.13
ClinPred		0.047	T
GERP RS		-9.7
Varity_R		0.030
gMVP		0.083

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-82111740;