rs2179638

Variant names:

• chr20-25224395-C-A
• rs2179638
• NM_001247.5:c.1243+238C>A

Your query was ambiguous. Multiple possible variants found:

• chr20-25224395-C-A
• chr20-25224395-C-G
• chr20-25224395-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001247.5(ENTPD6):​c.1243+238C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000792 in 378,680 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000044 (0 hom.)
• Consequence: ENTPD6 NM_001247.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 5 publications found

Genes affected

ENTPD6 (HGNC:3368): (ectonucleoside triphosphate diphosphohydrolase 6) ENTPD6 is similar to E-type nucleotidases (NTPases). NTPases, such as CD39, mediate catabolism of extracellular nucleotides. ENTPD6 contains 4 apyrase-conserved regions which are characteristic of NTPases. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001247.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTPD6	NM_001247.5	MANE Select	c.1243+238C>A		intron	N/A	NP_001238.3
	ENTPD6	NM_001322378.2		c.1243+238C>A		intron	N/A	NP_001309307.2
	ENTPD6	NM_001317941.3		c.1240+238C>A		intron	N/A	NP_001304870.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTPD6	ENST00000376652.9	TSL:1 MANE Select	c.1243+238C>A		intron	N/A	ENSP00000365840.4
	ENTPD6	ENST00000360031.6	TSL:1	c.1240+238C>A		intron	N/A	ENSP00000353131.2
	ENTPD6	ENST00000354989.10	TSL:1	c.1159+238C>A		intron	N/A	ENSP00000347084.6

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152128 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

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 AF: 0.00000441 AC: 1 AN: 226552 Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0 AN XY: 117464

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 6610

American (AMR) AF: 0.000149 AC: 1 AN: 6700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8240

East Asian (EAS) AF: 0.00 AC: 0 AN: 18362

South Asian (SAS) AF: 0.00 AC: 0 AN: 13496

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1098

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 140470

Other (OTH) AF: 0.00 AC: 0 AN: 14184

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152128 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74308

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000241 AC: 1 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2094

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 183

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.65
DANN	Benign	0.78
PhyloP100		-1.2

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: rs2179638; hg19: chr20-25205031;