rs1268055

Variant names:

• chr6-108861741-C-T
• rs1268055
• NM_032131.6:c.291+3470C>T

Variant summary

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

The NM_032131.6(ARMC2):​c.291+3470C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 151,932 control chromosomes in the GnomAD database, including 19,702 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 0.50 (19702 hom., cov: 31)
• Consequence: ARMC2 NM_032131.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.469
• Publications: 4 publications found

Genes affected

ARMC2 (HGNC:23045): (armadillo repeat containing 2) Involved in sperm axoneme assembly. Implicated in spermatogenic failure 38. [provided by Alliance of Genome Resources, Apr 2022]

ARMC2 Gene-Disease associations (from GenCC):

• spermatogenic failure 38

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMC2	NM_032131.6	c.291+3470C>T		intron_variant	Intron 3 of 17	ENST00000392644.9	NP_115507.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARMC2	ENST00000392644.9	c.291+3470C>T		intron_variant	Intron 3 of 17	1	NM_032131.6	ENSP00000376417.4
ARMC2	ENST00000368972.7	c.-204-7083C>T		intron_variant	Intron 2 of 16	2		ENSP00000357968.3
ARMC2	ENST00000237512.4	c.291+3470C>T		intron_variant	Intron 3 of 4	2		ENSP00000237512.4

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76477 AN: 151812 Hom.: 19694 Cov.: 31

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.504 AC: 76531 AN: 151932 Hom.: 19702 Cov.: 31 AF XY: 0.500 AC XY: 37144 AN XY: 74248

African (AFR) AF: 0.497 AC: 20587 AN: 41398

American (AMR) AF: 0.482 AC: 7354 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1979 AN: 3470

East Asian (EAS) AF: 0.255 AC: 1317 AN: 5162

South Asian (SAS) AF: 0.376 AC: 1811 AN: 4812

European-Finnish (FIN) AF: 0.585 AC: 6171 AN: 10548

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.526 AC: 35728 AN: 67956

Other (OTH) AF: 0.458 AC: 966 AN: 2110

Alfa AF: 0.513 Hom.: 33542

Bravo AF: 0.495

Asia WGS AF: 0.341 AC: 1185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.93
DANN	Benign	0.72
PhyloP100		-0.47
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: rs1268055; hg19: chr6-109182944;