1-151838437-G-T

Position:

• chr1-151838437-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001394591.1(C2CD4D):​c.553C>A​(p.Arg185Ser) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: C2CD4D NM_001394591.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.10

Genes affected

C2CD4D (HGNC:37210): (C2 calcium dependent domain containing 4D)

C2CD4D-AS1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35132045).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C2CD4D	NM_001394591.1	c.553C>A	p.Arg185Ser	missense_variant	2/2	ENST00000694868.1	NP_001381520.1
C2CD4D-AS1	NR_024237.2	n.161G>T		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C2CD4D	ENST00000694868.1	c.553C>A	p.Arg185Ser	missense_variant	2/2		NM_001394591.1	ENSP00000511551	P1
C2CD4D	ENST00000454109.1	c.553C>A	p.Arg185Ser	missense_variant	2/2	2		ENSP00000389554	P1
C2CD4D	ENST00000694869.1	c.553C>A	p.Arg185Ser	missense_variant	2/2			ENSP00000511552	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1263594 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 620726

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

May 28, 2024

The c.553C>A (p.R185S) alteration is located in exon 2 (coding exon 1) of the C2CD4D gene. This alteration results from a C to A substitution at nucleotide position 553, causing the arginine (R) at amino acid position 185 to be replaced by a serine (S). 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	0.19
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T
Eigen	Benign	0.14
Eigen_PC	Benign	-0.011
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	0.72	N
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.097
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.21
MutPred		0.27		Gain of glycosylation at R185 (P = 0.0016);
MVP		0.21
ClinPred		0.92	D
GERP RS		2.9
Varity_R		0.27
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: chr1-151810913;