chr1-244970326-C-CCCTCT

Variant names:

• chr1-244970326-C-CCCTCT
• rs78699431
• NM_032328.4:c.-90-3_-90-2insCCTCT

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_Strong

The NM_032328.4(DRC8):​c.-90-3_-90-2insCCTCT variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 20)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DRC8 NM_032328.4 splice_acceptor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• Publications: 3 publications found

Genes affected

DRC8 (HGNC:28166): (EF-hand calcium binding domain 2) The gene encodes a protein that contains two EF-hand calcium-binding domains although its function has yet to be determined. Alternatively spliced transcripts have been observed. [provided by RefSeq, Mar 2014]

LOC124900416 (HGNC:):

EFCAB2-AS1 (HGNC:58101):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.23517382 fraction of the gene. Cryptic splice site detected, with MaxEntScore 11, offset of 0 (no position change), new splice context is: cggcccctcctcccctctAGgcc. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032328.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRC8	NM_032328.4	MANE Select	c.-90-3_-90-2insCCTCT		splice_acceptor intron	N/A	NP_115704.1	Q5VUJ9-2
	EFCAB2-AS1	NR_111907.1		n.59-348_59-347insAGAGG		intron	N/A
	DRC8	NM_001290327.2		c.-175_-174insCCTCT		upstream_gene	N/A	NP_001277256.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB2	ENST00000366523.6	TSL:3 MANE Select	c.-90-3_-90-2insCCTCT		splice_acceptor intron	N/A	ENSP00000355480.1	Q5VUJ9-2
	EFCAB2	ENST00000447569.6	TSL:2	c.-93_-92insCCTCT		5_prime_UTR	Exon 1 of 7	ENSP00000408661.2	Q5VUJ9-3
	EFCAB2	ENST00000923177.1		c.-93_-92insCCTCT		5_prime_UTR	Exon 1 of 6	ENSP00000593236.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151702 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1345258 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 665630

African (AFR) AF: 0.00 AC: 0 AN: 29802

American (AMR) AF: 0.00 AC: 0 AN: 35130

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24502

East Asian (EAS) AF: 0.00 AC: 0 AN: 33820

South Asian (SAS) AF: 0.00 AC: 0 AN: 77954

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5580

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1047764

Other (OTH) AF: 0.00 AC: 0 AN: 56516

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151702 Hom.: 0 Cov.: 20 AF XY: 0.0000135 AC XY: 1 AN XY: 74048

African (AFR) AF: 0.00 AC: 0 AN: 41308

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5110

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67848

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.5
Mutation Taster		=158/42	disease causing (fs/PTC)

Splicing

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

Other links and lift over

dbSNP: rs78699431; hg19: chr1-245133628;