chr16-57698010-G-A

Variant names:

• chr16-57698010-G-A
• rs147737491
• NM_001289162.2:c.61G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001289162.2(DRC7):​c.61G>A​(p.Glu21Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,613,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: DRC7 NM_001289162.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.56
• Publications: 1 publications found

Genes affected

DRC7 (HGNC:25289): (dynein regulatory complex subunit 7) Predicted to be involved in flagellated sperm motility. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000260467 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.079562694).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001289162.2. 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
	DRC7	NM_001289162.2	MANE Select	c.61G>A	p.Glu21Lys	missense	Exon 3 of 19	NP_001276091.1	Q8IY82-1
	DRC7	NM_032269.6		c.61G>A	p.Glu21Lys	missense	Exon 2 of 18	NP_115645.4
	DRC7	NM_001289163.2		c.61G>A	p.Glu21Lys	missense	Exon 2 of 17	NP_001276092.1	Q8IY82-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRC7	ENST00000360716.8	TSL:1 MANE Select	c.61G>A	p.Glu21Lys	missense	Exon 3 of 19	ENSP00000353942.3	Q8IY82-1
	DRC7	ENST00000394337.8	TSL:1	c.61G>A	p.Glu21Lys	missense	Exon 2 of 18	ENSP00000377869.4	Q8IY82-1
	DRC7	ENST00000871948.1		c.61G>A	p.Glu21Lys	missense	Exon 3 of 19	ENSP00000542007.1

Frequencies

GnomAD3 genomes AF: 0.0000985 AC: 15 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000123 AC: 31 AN: 251216 AF XY: 0.000155

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000158

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000117 AC: 171 AN: 1461522 Hom.: 0 Cov.: 31 AF XY: 0.000113 AC XY: 82 AN XY: 727030

African (AFR) AF: 0.0000896 AC: 3 AN: 33474

American (AMR) AF: 0.000224 AC: 10 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53326

Middle Eastern (MID) AF: 0.000900 AC: 5 AN: 5554

European-Non Finnish (NFE) AF: 0.000132 AC: 147 AN: 1112006

Other (OTH) AF: 0.0000828 AC: 5 AN: 60368

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152208 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74358

African (AFR) AF: 0.0000241 AC: 1 AN: 41464

American (AMR) AF: 0.0000655 AC: 1 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68042

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

Alfa AF: 0.000134 Hom.: 0

Bravo AF: 0.0000831

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.000157 AC: 19

EpiCase AF: 0.000327

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.6
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.082
Sift	Benign	0.043	D
Sift4G	Benign	0.20	T
Polyphen		0.014	B
Vest4		0.29
MVP		0.36
MPC		0.19
ClinPred		0.17	T
GERP RS		3.0
Varity_R		0.10
gMVP		0.45
Mutation Taster		=95/5	polymorphism

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: rs147737491; hg19: chr16-57731922;