2-68132765-C-T

Variant names:

• chr2-68132765-C-T
• rs4078978
• NM_138458.4:c.867-1320G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138458.4(DNAAF10):​c.867-1320G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0671 in 152,270 control chromosomes in the GnomAD database, including 398 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.067 (398 hom., cov: 32)
• Consequence: DNAAF10 NM_138458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270
• Publications: 20 publications found

Genes affected

DNAAF10 (HGNC:25176): (dynein axonemal assembly factor 10) This gene encodes a protein with two WD40 repeat domains thought to be involved in an apoptosis via activation of caspase-3. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

ENSG00000273398 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.09 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF10	NM_138458.4	c.867-1320G>A		intron_variant	Intron 7 of 7	ENST00000295121.11	NP_612467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF10	ENST00000295121.11	c.867-1320G>A		intron_variant	Intron 7 of 7	1	NM_138458.4	ENSP00000295121.6
ENSG00000273398	ENST00000406334.3	n.*884-1320G>A		intron_variant	Intron 14 of 14	2		ENSP00000384974.3

Frequencies

GnomAD3 genomes AF: 0.0671 AC: 10205 AN: 152152 Hom.: 392 Cov.: 32

Gnomad AFR AF: 0.0403

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0836

Gnomad ASJ AF: 0.0959

Gnomad EAS AF: 0.00577

Gnomad SAS AF: 0.0978

Gnomad FIN AF: 0.0640

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.0806

Gnomad OTH AF: 0.0885

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0671 AC: 10216 AN: 152270 Hom.: 398 Cov.: 32 AF XY: 0.0668 AC XY: 4976 AN XY: 74444

African (AFR) AF: 0.0402 AC: 1671 AN: 41538

American (AMR) AF: 0.0834 AC: 1276 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0959 AC: 333 AN: 3472

East Asian (EAS) AF: 0.00578 AC: 30 AN: 5188

South Asian (SAS) AF: 0.0972 AC: 469 AN: 4824

European-Finnish (FIN) AF: 0.0640 AC: 679 AN: 10604

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.0805 AC: 5479 AN: 68022

Other (OTH) AF: 0.0956 AC: 202 AN: 2112

Alfa AF: 0.0789 Hom.: 2073

Bravo AF: 0.0666

Asia WGS AF: 0.100 AC: 346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.83
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4078978; hg19: chr2-68359897;